2025/05/06 更新

写真a

キクチ　マサタカ
菊地　正隆
KIKUCHI Masataka
所属
脳研究所 生命科学リソース研究センター 遺伝子機能解析学 特任准教授
職名
特任准教授
外部リンク

学位

  • 博士（医学） （ 2013年3月   東京医科歯科大学 ）

研究分野

  • ライフサイエンス / システムゲノム科学

経歴（researchmap）

  • 大阪大学   大学院医学系研究科   招へい准教授

    2022年4月 - 現在

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  • 東京大学 大学院新領域創成科学研究科 メディカルゲノム専攻   特任准教授

    2022年4月 - 2024年3月

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  • 大阪大学   大学院医学系研究科   特任准教授

    2020年5月 - 2022年3月

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  • 特定非営利活動法人システム・バイオロジー研究機構   客員研究員

    2019年9月 - 2023年3月

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  • 国立精神・神経医療研究センター   精神保健研究所 精神疾患病態研究部   客員研究員

    2018年12月 - 現在

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  • 大阪大学   ゲノム情報学共同研究講座   特任講師

    2018年10月 - 2020年4月

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  • 大阪大学   ゲノム情報学共同研究講座   特任助教

    2015年4月 - 2018年9月

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  • 新潟大学   遺伝子機能解析学   研究員

    2013年3月 - 2015年3月

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▶ 全件表示

経歴

  • 新潟大学   脳研究所 生命科学リソース研究センター 遺伝子機能解析学   特任准教授

    2025年4月 - 現在

  • 新潟大学   脳研究所 生命科学リソース研究センター 遺伝子機能解析学   特任准教授

    2024年4月 - 2025年3月

 

論文

  • Schizophrenia-related Xpo7 haploinsufficiency leads to behavioral and nuclear transport pathologies 査読

    Saori Toyoda, Masataka Kikuchi (co-first), Yoshifumi Abe, Kyosei Tashiro, Takehisa Handa, Shingo Katayama, Yukiko Motokawa, Kenji F Tanaka, Hidehiko Takahashi, Hiroki Shiwaku

    EMBO Reports   2025年1月

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    担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

    Abstract

    Recent genetic studies by the Schizophrenia Exome Sequencing Meta-Analysis (SCHEMA) consortium have identified that protein-truncating variants of exportin 7 (XPO7) can increase the risk of schizophrenia (odds ratio, 28.1). Here we show that mice with Xpo7 haploinsufficiency (Xpo7<sup>+/−</sup> mice) present with cognitive and social behavioral impairments. Through proteome analysis using immunoprecipitation and frontal cortex nuclear isolation of Xpo7<sup>+/−</sup> mice, we identify 45 molecules interacting with Xpo7, including CutC, Rbfox3, and Gria3. Through single-nucleus RNA sequencing of the frontal cortex and striatum of Xpo7<sup>+/−</sup> mice differentiating between the onset and progressive stages, we also identify 284 gene expression changes that correlate with these stages. These genes encompass high-odds risk genes of schizophrenia identified by SCHEMA, including Gria3, Grin2A, Herc1, and Trio. Furthermore, our approach reveals 15 gene expression changes in the frontal cortex that correlate with the progressive stages. Our findings indicate the importance of investigating whether the interactions among the high-risk genes identified by SCHEMA contribute to a common schizophrenia pathology and underscore the significance of stage-dependent analysis.

    DOI： 10.1038/s44319-024-00362-9

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    その他リンク： https://www.embopress.org/doi/full/10.1038/s44319-024-00362-9

  • Tau Accumulation Induces Microglial State Alterations in Alzheimer's Disease Model Mice 査読

    Kenichi Nagata, Shoko Hashimoto, Daisuke Joho, Ryo Fujioka, Yukio Matsuba, Misaki Sekiguchi, Naomi Mihira, Daisuke Motooka, Yu-Chen Liu, Daisuke Okuzaki, Masataka Kikuchi, Shigeo Murayama, Takaomi C. Saido, Hiroshi Kiyama, Hiroki Sasaguri

    eNeuro   11 ( 12 )   ENEURO.0260 - 24.2024   2024年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1523/eneuro.0260-24.2024

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  • アルツハイマー病のポリジェニックリスクスコア層別化によるマルチオミックス解析

    菊地 正隆, 宮下 哲典, 廣田 湧, 原 範和, 長谷川 舞衣, 榊原 泰史, 関谷 倫子, 齊藤 祐子, 村山 繁雄, 飯島 浩一, 池内 健

    Dementia Japan   38 ( 4 )   723 - 723   2024年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • Cortical similarities in psychiatric and mood disorders identified in federated VBM analysis via COINSTAC 査読

    Kelly Rootes-Murdy, Sandeep Panta, Ross Kelly, Javier Romero, Yann Quidé, Murray J. Cairns, Carmel Loughland, Vaughan J. Carr, Stanley V. Catts, Assen Jablensky, Melissa J. Green, Frans Henskens, Dylan Kiltschewskij, Patricia T. Michie, Bryan Mowry, Christos Pantelis, Paul E. Rasser, William R. Reay, Ulrich Schall, Rodney J. Sco, Oliver J. Watkeys, Gloria Roberts, Philip B. Mitchell, Janice M. Fullerton, Bronwyn J. Overs, Masataka Kikuchi, Ryota Hashimoto, Junya Matsumoto, Masaki Fukunaga, Perminder S. Sachdev, Henry Brodaty, Wei Wen, Jiyang Jiang, Negar Fani, Timothy D. Ely, Adriana Lorio, Jennifer S. Stevens, Kerry Ressler, Tanja Jovanovic, Sanne J.H. van Rooij, Lydia M. Federmann, Christiane Jockwitz, Alexander Teumer, Andreas J. Forstner, Svenja Caspers, Sven Cichon, Sergey M. Plis, Anand D. Sarwate, Vince D. Calhoun

    Patterns   100987 - 100987   2024年5月

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    掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.patter.2024.100987

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  • Gene-gene functional relationships in Alzheimer’s disease: CELF1 regulates KLC1 alternative splicing 査読

    Masataka Kikuchi, Justine Vie, Kenichi Nagata, Masahiro Sato, Geraldine David, Audic Yann, Michael A. Silverman, Mitsuko Yamamoto, Hiroyasu Akatsu, Yoshio Hashizume, Shuko Takeda, Shoshin Akamine, Tesshin Miyamoto, Ryota Uozumi, Shiho Gotoh, Kohji Mori, Manabu Ikeda, Luc Paillard, Takashi Morihara

    Biochemical and Biophysical Research Communications   150025 - 150025   2024年4月

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    担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.bbrc.2024.150025

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  • Polygenic effects on the risk of Alzheimer’s disease in the Japanese population 査読

    Masataka Kikuchi, Akinori Miyashita, Norikazu Hara, Kensaku Kasuga, Yuko Saito, Shigeo Murayama, Akiyoshi Kakita, Hiroyasu Akatsu, Kouichi Ozaki, Shumpei Niida, Ryozo Kuwano, Takeshi Iwatsubo, Akihiro Nakaya, Takeshi Ikeuchi, Michael W. Weiner, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, Laurel Beckett, Robert C. Green, John Morris, Leslie M. Shaw, Beau Ances, John C. Morris, Maria Carroll, Mary L. Creech, Erin Franklin, Mark A. Mintun, Stacy Schneider, Angela Oliver, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Rachelle S. Doody, Javier Villanueva-Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Daniel Marson, Randall Griffith, David Clark, David Geldmacher, John Brockington, Erik Roberson, Marissa Natelson Love, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Daniel Varon, Maria T. Greig, Peggy Roberts, Marilyn Albert, Chiadi Onyike, Daniel D’Agostino, Stephanie Kielb, James E. Galvin, Brittany Cerbone, Christina A. Michel, Dana M. Pogorelec, Henry Rusinek, Mony J. de Leon, Lidia Glodzik, Susan De Santi, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Ruth A. Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Cynthia Hunt, Kathleen Tingus, Ellen Woo, Daniel H. S. Silverman, Po H. Lu, George Bartzokis, Neill R. Graff-Radford, Francine Parfitt, Tracy Kendall, Heather Johnson, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Howard Feldman, Benita Mudge, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek Marsel Mesulam, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T.-Y. Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Anna Burke, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Anahita Adeli, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Leslie Gordineer, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Henry Querfurth, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Norman Relkin, Gloria Chaing, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Takashi Asada, Hiroyuki Arai, Morihiro Sugishita, Hiroshi Matsuda, Noriko Sato, Hajime Sato, Kengo Ito, Teruhiko Kachi, Kenji Toba, Michio Senda, Kenji Ishii, Shun Shimohama, Masaki Saitoh, Rika Yamauchi, Takashi Hayashi, Chiyoko Takanami, Seiju Kobayashi, Norihito Nakano, Junichiro Kanazawa, Takeshi Ando, Masato Hareyama, Masamitsu Hatakenaka, Eriko Tsukamoto, Shinji Ochi, Mikio Shoji, Etsuro Matsubara, Takeshi Kawarabayashi, Yasuhito Wakasaya, Takashi Nakata, Naoko Nakahata, Shuichi Ono, Yoshihiro Takai, Satoshi Takahashi, Hisashi Yonezawa, Junko Takahashi, Masako Kudoh, Kuniko Ueno, Hiromi Sakashita, Kuniko Watanabe, Makoto Sasaki, Yutaka Matsumura, Yohsuke Hirata, Tsuyoshi Metoki, Susumu Hayakawa, Yuichi Sato, Masayuki Takeda, Koichiro Sera, Kazunori Terasaki, Toshiaki Sasaki, Yoshihiro Saitoh, Shoko Goto, Ken Nagata, Tetsuya Maeda, Yasushi Kondoh, Takashi Yamazaki, Daiki Takano, Mio Miyata, Hiromi Komatsu, Mayumi Watanabe, Tomomi Sinoda, Rena Muraoka, Kayoko Kikuchi, Hitomi Ito, Aki Sato, Toshibumi Kinoshita, Hideyo Toyoshima, Kaoru Sato, Shigeki Sugawara, Isao Ito, Fumiko Kumagai, Katsutoshi Furukawa, Masaaki Waragai, Naoki Tomita, Mari Ootsuki, Katsumi Sugawara, Satomi Sugawara, Nobuyuki Okamura, Shunji Mugikura, Atsushi Umetsu, Takanori Murata, Tatsuo Nagasaka, Yukitsuka Kudo, Manabu Tashiro, Shoichi Watanuki, Masatoyo Nishizawa, Takayoshi Tokutake, Saeri Ishikawa, Emiko Kishida, Nozomi Sato, Mieko Hagiwara, Kumi Yamanaka, Takeyuki Watanabe, Taeko Takasugi, Shoichi Inagawa, Kenichi Naito, Masanori Awaji, Tsutomu Kanazawa, Kouiti Okamoto, Masaki Ikeda, Yuiti Tasiro, Syunn Nagamine, Sathiko Kurose, Tsuneo Yamazaki, Shiori Katsuyama, Sayuri Fukushima, Etsuko Koya, Makoto Amanuma, Kouiti Ujita, Kazuhiro Kishi, Kazuhisa Tuda, Noboru Oriuti, Katsuyoshi Mizukami, Tetsuaki Arai, Etsuko Nakajima, Katsumi Miyamoto, Tomoya Kobayashi, Saori Itoya, Jun Ookubo, Toshiya Akatsu, Yoshiko Anzai, Junya Ikegaki, Yuuichi Katou, Kaori Kimura, Hajime Saitou, Kazuya Shinoda, Satoka Someya, Hiroko Taguchi, Kazuya Tashiro, Masaya Tanaka, Tatsuya Nemoto, Ryou Wakabayashi, Daisuke Watanabe, Kousaku Saotome, Ryou Kuchii, Harumasa Takano, Tetsuya Suhara, Hitoshi Shinoto, Hitoshi Shimada, Makoto Higuchi, Takaaki Mori, Hiroshi Ito, Takayuki Obata, Yoshiko Fukushima, Kazuko Suzuki, Izumi Izumida, Katsuyuki Tanimoto, Takahiro Shiraishi, Hitoshi Shinotoh, Junko Shiba, Hiroaki Yano, Miki Satake, Aimi Nakui, Yae Ebihara, Tomomi Hasegawa, Yasumasa Yoshiyama, Mami Kato, Yuki Ogata, Hiroyuki Fujikawa, Nobuo Araki, Yoshihiko Nakazato, Takahiro Sasaki, Tomokazu Shimadu, Kimiko Yoshimaru, Etsuko Imabayashi, Asako Yasuda, Keiko Ozawa, Etuko Yamamoto, Natsumi Nakamata, Noriko Miyauchi, Rieko Hashimoto, Taishi Unezawa, Takafumi Ichikawa, Hiroki Hayashi, Masakazu Yamagishi, Tunemichi Mihara, Masaya Hirano, Shinichi Watanabe, Junichiro Fukuhara, Hajime Matsudo, Nobuyuki Saito, Atsushi Iwata, Hisatomo Kowa, Toshihiro Hayashi, Ryoko Ihara, Toji Miyagawa, Mizuho Yoshida, Yuri Koide, Eriko Samura, Kurumi Fujii, Kaori Watanabe, Nagae Orihara, Toshimitsu Momose, Miwako Takahashi, Takuya Arai, Yoshiki Kojima, Akira Kunimatsu, Harushi Mori, Masami Goto, Takeo Sarashina, Syuichi Uzuki, Seiji Katou, Yoshiharu Sekine, Yukihiro Takauchi, Chiine Kagami, Kazutomi Kanemaru, Yasushi Nishina, Maria Sakaibara, Yumiko Okazaki, Rieko Okada, Maki Obata, Masaki Takao, Yuko Iwata, Mizuho Minami, Yasuko Hanabusa, Hanae Shingyouji, Kyoko Tottori, Aya Tokumaru, Makoto Ichinose, Kazuya Kume, Syunsuke Kahashi, Kunimasa Arima, Shin Tanaka, Yuko Nagahusa, Masuhiro Sakata, Mitsutoshi Okazaki, Maki Yamada, Tadashi Tukamoto, Tiine Kodama, Tomoko Takeuchi, Keiichiro Ozawa, Yoshiko Kawaji, Kyouko Tottori, Yasuhiro Nakata, Satoshi Sawada, Makoto Mimatsu, Daisuke Nakkamura, Takeshi Tamaru, Shunichirou Horiuchi, Heii Arai, Tsuneyoshi Ota, Aiko Kodaka, Yuko Tagata, Tomoko Nakada, Eizo Iseki, Kiyoshi Sato, Hiroshige Fujishiro, Norio Murayama, Masaru Suzuki, Satoshi Kimura, Masanobu Takahashi, Haruo Hanyu, Hirofumi Sakurai, Takahiko Umahara, Hidekazu Kanetaka, Kaori Arashino, Mikako Murakami, Ai Kito, Seiko Miyagi, Kaori Doi, Kazuyoshi Sasaki, Mineo Yamazaki, Akiko Ishiwata, Yasushi Arai, Akane Nogami, Sumiko Fukuda, Koichi Kozaki, Yukiko Yamada, Sayaka Kimura, Ayako Machida, Kuninori Kobayashi, Hidehiro Mizusawa, Nobuo Sanjo, Mutsufusa Watanabe, Takuya Ohkubo, Hiromi Utashiro, Yukiko Matsumoto, Kumiko Hagiya, Yoshiko Miyama, Hitoshi Shibuya, Isamu Ohashi, Akira Toriihara, Takako Shinozaki, Haruko Hiraki, Shinichi Ohtani, Toshifumi Matsui, Tomomi Toyama, Hideki Sakurai, Kumiko Sugiura, Yu Hayasaka, Hirofumi Taguchi, Shizuo Hatashita, Akari Imuta, Akiko Matsudo, Daichi Wakebe, Hideki Hayakawa, Mitsuhiro Ono, Takayoshi Ohara, Yukihiko Washimi, Yutaka Arahata, Akinori Takeda, Akiko Yamaoka, Masashi Tsujimoto, Takiko Kawai, Ai Honda, Yoko Konagaya, Hideyuki Hattori, Kenji Yoshiyama, Rina Miura, Takashi Sakurai, Miura Hisayuki, Hidetoshi Endou, Syousuke Satake, Young Jae Hong, Katsunari Iwai, Masaki Suenaga, Sumiko Morita, Kengo Itou, Takashi Kato, Ken Fujiwara, Rikio Katou, Mariko Koyama, Naohiko Fukaya, Akira Tsuji, Hitomi Shimizu, Hiroyuki Fujisawa, Tomoko Nakazawa, Satoshi Koyama, Takanori Sakata, Masahito Yamada, Mitsuhiro Yoshita, Miharu Samuraki, Kenjiro Ono, Moeko Shinohara, Yuki Soshi, Kozue Niwa, Chiaki Doumoto, Mariko Hata, Miyuki Matsushita, Mai Tsukiyama, Nozomi Takeda, Sachiko Yonezawa, Ichiro Matsunari, Osamu Matsui, Fumiaki Ueda, Yasuji Ryu, Masanobu Sakamoto, Yasuomi Ouchi, Yumiko Fujita, Madoka Chita, Rika Majima, Hiromi Tsubota, Umeo Shirasawa, Masashi Sugimori, Wataru Ariya, Yuuzou Hagiwara, Yasuo Tanizaki, Hidenao Fukuyama, Shizuko Tanaka-Urayama, Shin-Ichi Urayama, Ryosuke Takahashi, Kengo Uemura, Hajime Takechi, Chihiro Namiki, Takeshi Kihara, Hiroshi Yamauchi, Emiko Maeda, Natsu Saito, Shiho Satomi, Konomi Kabata, Tomohisa Okada, Koichi Ishizu, Shigeto Kawase, Satoshi Fukumoto, Masanori Nakagawa, Masaki Kondo, Fumitoshi Niwa, Toshiki Mizuno, Yoko Oishi, Mariko Yamazaki, Daisuke Yamaguchi, Takahiko Tokuda, Kyoko Ito, Yoku Asano, Chizuru Hamaguchi, Kei Yamada, Chio Okuyama, Kentaro Akazawa, Shigenori Matsushima, Takamasa Matsuo, Toshiaki Nakagawa, Takeshi Nii, Takuji Nishida, Kuniaki Kiuchi, Masami Fukusumi, Hideyuki Watanabe, Toshiaki Taoka, Akihiro Nogi, Masatoshi Takeda, Toshihisa Tanaka, Hiroaki Kazui, Takashi Kudo, Masayasu Okochi, Takashi Morihara, Shinji Tagami, Masahiko Takaya, Tamiki Wada, Mikiko Yokokoji, Hiromichi Sugiyama, Daisuke Yamamoto, Keiko Nomura, Mutsumi Tomioka, Naoyuki Sato, Noriyuki Hayashi, Shuko Takeda, Eiichi Uchida, Yoshiyuki Ikeda, Mineto Murakami, Takami Miki, Hiroyuki Shimada, Suzuka Ataka, Akitoshi Takeda, Yuki Iwamoto, Motokatsu Kanemoto, Jun Takeuchi, Rie Azuma, Naomi Tagawa, Junko Masao, Yuka Matsumoto, Yuko Kikukawa, Hisako Fujii, Junko Matsumura, Susumu Shiomi, Joji Kawabe, Yoshihiro Shimonishi, Mitsuji Higashida, Tomohiro Sahara, Takashi Yamanaga, Yukio Miki, Shinichi Sakamoto, Hiroyuki Tsushima, Kiyoshi Maeda, Yasuji Yamamoto, Kazuo Sakai, Haruhiko Oda, Yoshihiko Tahara, Toshio Kawamata, Taichi Akisaki, Mizuho Adachi, Masako Kuranaga, Sachi Takegawa, Seishi Terada, Yuki Kishimoto, Naoya Takeda, Nao Imai, Mayumi Yabe, Reiko Wada, Takeshi Ishihara, Hajime Honda, Osamu Yokota, Kentaro Ida, Daigo Anami, Seiji Inoue, Toshi Matsushita, Shinsuke Hiramatsu, Hiromi Tonbara, Reiko Yamamoto, Kenji Nakashima, Kenji Wada-Isoe, Saori Yamasaki, Eijiro Yamashita, Yu Nakamura, Ichiro Ishikawa, Sonoko Danjo, Tomomi Shinohara, Yuka Kashimoto, Miyuki Ueno, Yoshihiro Nishiyama, Yuka Yamamoto, Narihide Kimura, Kazuo Ogawa, Yasuhiro Sasakawa, Takashi Ishimori, Yukito Maeda, Tatsuo Yamada, Shinji Ouma, Aika Fukuhara-Kaneumi, Nami Sakamoto, Rie Nagao, Kengo Yoshimitsu, Yasuo Kuwabara, Ryuji Nakamuta, Minoru Tanaka, Manabu Ikeda, Yuusuke Yatabe, Mamoru Hashimoto, Keiichirou Kaneda, Kazuki Honda, Naoko Ichimi, Mariko Morinaga, Miyako Noda, Fumi Akatuka, Mika Kitajima, Toshinori Hirai, Shinya Shiraishi, Naoji Amano, Shinsuke Washizuka, Tetsuya Hagiwara, Yatsuka Okada, Tomomi Ogihara, Toru Takahashi, Shin Inuzuka, Nobuhiro Sugiyama, Takehiko Yasaki, Minori Kitayama, Tomonori Owa, Akiko Ryokawa, Rie Takeuchi, Satoe Goto, Keiko Yamauchi, Mie Ito, Tomoki Kaneko, Hitoshi Ueda, Shuichi Ikeda, Ban Mihara, Hirofumi Kubo, Akiko Takano, Gou Yasui, Masami Akuzawa, Kaori Yamaguchi, Toshinari Odawara, Naomi Oota, Megumi Shimamura, Mikiko Sugiyama, Atsushi Watanabe, Shigeo Takebayashi, Yoshigazu Hayakawa, Mitsuhiro Idegawa, Noriko Toya, Kazunari Ishii

    Alzheimer's Research & Therapy   16 ( 1 )   2024年2月

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    担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1186/s13195-024-01414-x

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    その他リンク： https://link.springer.com/article/10.1186/s13195-024-01414-x/fulltext.html

  • ヒト肝癌由来HepG2細胞株におけるAPOEの機能解析

    大日方 藍, Liu Lixin, 原 範和, 長谷川 舞衣, 月江 珠緒, 五十嵐 一也, 幡野 敦, 角田 伸人, 菊地 正隆, 松本 雅記, 春日 健作, 宮下 哲典, 池内 健

    Dementia Japan   37 ( 4 )   678 - 678   2023年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • アルツハイマー連続体における脳脊髄液αシヌクレインの臨床的有用性の検討

    五十嵐 一也, 春日 健作, 月江 珠緒, 菊地 正隆, 宮下 哲典, 小野寺 理, 岩坪 威, 池内 健, Japanese Alzheimer's Disease Neuroimaging Initiative

    Dementia Japan   37 ( 4 )   687 - 687   2023年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • 日本人ADにおけるLATE,PARTの感受性遺伝子解析

    宮下 哲典, 金田 大太, 原 範和, 光森 理紗, 大日方 藍, 月江 珠緒, 長谷川 舞衣, 五十嵐 一也, 春日 健作, 菊地 正隆, 齊藤 祐子, 村山 繁雄, 橋詰 良夫, 新飯田 俊平, 尾崎 浩一, 池内 健

    Dementia Japan   37 ( 4 )   709 - 709   2023年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • 脳脊髄液アミロイドβ(Aβ)38の臨床的意義の検討

    月江 珠緒, 春日 健作, 菊地 正隆, 五十嵐 一也, 大滝 悠莉, 石黒 敬信, 宮下 哲典, 小野寺 理, 岩坪 威, 池内 健, J-ADNI

    Dementia Japan   37 ( 4 )   658 - 658   2023年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • Beyond the Global Brain Differences: Intra-individual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers 査読

    Rune Boen, Tobias Kaufmann, Dennis van der Meer, Oleksandr Frei, Ingrid Agartz, David Ames, Micael Andersson, Nicola J. Armstrong, Eric Artiges, Joshua R. Atkins, Jochen Bauer, Francesco Benedetti, Dorret I. Boomsma, Henry Brodaty, Katharina Brosch, Randy L. Buckner, Murray J. Cairns, Vince Calhoun, Svenja Caspers, Sven Cichon, Aiden P. Corvin, Benedicto Crespo Facorro, Udo Dannlowski, Friederike S. David, Eco J.C. de Geus, Greig I. de Zubicaray, Sylvane Desrivières, Joanne L. Doherty, Gary Donohoe, Stefan Ehrlich, Else Eising, Thomas Espeseth, Simon E. Fisher, Andreas J. Forstner, Lidia Fortaner Uyà, Vincent Frouin, Masaki Fukunaga, Tian Ge, David C. Glahn, Janik Goltermann, Hans J. Grabe, Melissa J. Green, Nynke A. Groenewold, Dominik Grotegerd, Tim Hahn, Ryota Hashimoto, Jayne Y. Hehir-Kwa, Frans A. Henskens, Avram J. Holmes, Asta K. Haberg, Jan Haavik, Sebastien Jacquemont, Andreas Jansen, Christiane Jockwitz, Erik G. Jonsson, Masataka Kikuchi, Tilo Kircher, Kuldeep Kumar, Stephanie Le Hellard, Costin Leu, David E. Linden, Jingyu Liu, Robert Loughnan, Karen A. Mather, Katie L. McMahon, Allan F. McRae, Sarah E. Medland, Susanne Meinert, Clara A. Moreau, Derek W. Morris, Bryan J. Mowry, Thomas W. Muhleisen, Igor Nenadić, Markus M. Nöthen, Lars Nyberg, Michael J. Owen, Marco Paolini, Tomas Paus, Zdenka Pausova, Karin Persson, Yann Quidé, Tiago Reis Marques, Perminder S. Sachdev, Sigrid B. Sando, Ulrich Schall, Rodney J. Scott, Geir Selbæk, Elena Shumskaya, Ana I. Silva, Sanjay M. Sisodiya, Frederike Stein, Dan J. Stein, Benjamin Straube, Fabian Streit, Lachlan T. Strike, Alexander Teumer, Lea Teutenberg, Anbupalam Thalamuthu, Paul A. Tooney, Diana Tordesillas-Gutierrez, Julian N. Trollor, Dennis van 't Ent, Marianne B.M. van den Bree, Neeltje E.M. van Haren, Javier Vazquez-Bourgon, Henry Volzke, Wei Wen, Katharina Wittfeld, Christopher R.K. Ching, Lars T. Westlye, Paul M. Thompson, Carrie E. Bearden, Kaja K. Selmer, Dag Alnæs, Ole A. Andreassen, Ida E. Sonderby

    Biological Psychiatry   2023年9月

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

    DOI： 10.1016/j.biopsych.2023.08.018

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  • The clinical application of optimized AT(N) classification in Alzheimer’s clinical syndrome (ACS) and non-ACS conditions 査読

    Kensaku Kasuga, Tamao Tsukie, Masataka Kikuchi, Takayoshi Tokutake, Kazuo Washiyama, Soichiro Shimizu, Hiroshi Yoshizawa, Yasuko Kuroha, Ryuji Yajima, Hiroshi Mori, Yasuaki Arakawa, Kiyoshi Onda, Akinori Miyashita, Osamu Onodera, Takeshi Iwatsubo, Takeshi Ikeuchi

    Neurobiology of Aging   127   23 - 32   2023年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.neurobiolaging.2023.03.007

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  • 【認知症のゲノム医療】APOEの遺伝型とレアミスセンスバリアント 臨床応用への可能性

    宮下 哲典, 原 範和, 春日 健作, 菊地 正隆, 尾崎 浩一, 新飯田 俊平, 他田 真理, 柿田 明美, 池内 健

    Dementia Japan   37 ( 2 )   239 - 249   2023年4月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • 網羅的遺伝子発現解析によるアルツハイマー病早期変動遺伝子の同定

    菊地 正隆, 廣田 湧, 原 範和, 榊原 泰史, 関谷 倫子, 宮下 哲典, 池内 健, 飯島 浩一

    老年精神医学雑誌   33 ( 増刊II )   225 - 225   2022年11月

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    記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

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  • 網羅的遺伝子発現解析によるアルツハイマー病早期変動遺伝子の同定

    菊地 正隆, 廣田 湧, 原 範和, 榊原 泰史, 関谷 倫子, 宮下 哲典, 池内 健, 飯島 浩一

    Dementia Japan   36 ( 4 )   743 - 743   2022年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • Identification of mild cognitive impairment subtypes predicting conversion to Alzheimer’s disease using multimodal data 査読

    Masataka Kikuchi, Kaori Kobayashi, Sakiko Itoh, Kensaku Kasuga, Akinori Miyashita, Takeshi Ikeuchi, Eiji Yumoto, Yuki Kosaka, Yasuto Fushimi, Toshihiro Takeda, Shirou Manabe, Satoshi Hattori, Alzheimer’s Disease Neuroimaging Initiative, Akihiro Nakaya, Kenichi Kamijo, Yasushi Matsumura

    Computational and Structural Biotechnology Journal   20   5296 - 5308   2022年8月

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    担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.csbj.2022.08.007

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  • Construction of prediction models for growth traits of soybean cultivars based on phenotyping in diverse genotype and environment combinations 査読 国際誌

    Andi Madihah Manggabarani, Takuyu Hashiguchi, Masatsugu Hashiguchi, Atsushi Hayashi, Masataka Kikuchi, Yusdar Mustamin, Masaru Bamba, Kunihiro Kodama, Takanari Tanabata, Sachiko Isobe, Hidenori Tanaka, Ryo Akashi, Akihiro Nakaya, Shusei Sato

    DNA Research   29 ( 4 )   2022年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

    Abstract

    As soybean cultivars are adapted to a relatively narrow range of latitude, the effects of climate changes are estimated to be severe. To address this issue, it is important to improve our understanding of the effects of climate change by applying the simulation model including both genetic and environmental factors with their interactions (G×E). To achieve this goal, we conducted the field experiments for soybean core collections using multiple sowing times in multi-latitudinal fields. Sowing time shifts altered the flowering time (FT) and growth phenotypes, and resulted in increasing the combinations of genotypes and environments. Genome-wide association studies for the obtained phenotypes revealed the effects of field and sowing time to the significance of detected alleles, indicating the presence of G×E. By using accumulated phenotypic and environmental data in 2018 and 2019, we constructed multiple regression models for FT and growth pattern. Applicability of the constructed models was evaluated by the field experiments in 2020 including a novel field, and high correlation between the predicted and measured values was observed, suggesting the robustness of the models. The models presented here would allow us to predict the phenotype of the core collections in a given environment.

    DOI： 10.1093/dnares/dsac024

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    その他リンク： https://academic.oup.com/dnaresearch/article-pdf/29/4/dsac024/45283501/dsac024.pdf

  • Different AT(N) profiles and clinical progression classified by two different N markers using total tau and neurofilament light chain in cerebrospinal fluid 査読 国際誌

    Kensaku Kasuga†, Masataka Kikuchi†, Tamao Tsukie, Kazushi Suzuki, Ryoko Ihara, Atsushi Iwata, Norikazu Hara, Akinori Miyashita, Ryozo Kuwano, Takeshi Iwatsubo, Takeshi Ikeuchi, Alzheimer’s Disease Neuroimaging Initiative

    BMJ Neurology Open   (in press) ( 2 )   e000321   2022年7月

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    担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1136/bmjno-2022-000321

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  • Genetics of Alzheimer’s disease: an East Asian perspective 査読 国際誌

    Akinori Miyashita†, Masataka Kikuchi†, Norikazu Hara†, Takeshi Ikeuchi

    Journal of Human Genetics   2022年6月

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    担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

    Abstract

    Alzheimer’s disease (AD) is an age-related multifactorial neurodegenerative disorder. Advances in genome technology, including next generation sequencing have uncovered complex genetic effects in AD by analyzing both common and rare functional variants. Multiple lines of evidence suggest that the pathogenesis of AD is influenced by multiple genetic components rather than single genetic factor. Previous genetic studies on AD have predominantly included European ancestry cohorts; hence, the non-European population may be underrepresented, potentially leading to reduced diversity in AD genetic research. Additionally, ethnic diversity may result in dissimilar effects of genetic determinants in AD. APOE genotypes are a well-established genetic risk factor in AD, with the East Asian population having a higher risk of AD associated with the APOE ε4 allele. To date, seven genome-wide association studies (GWAS) have been conducted in East Asians, which report a total of 26 AD-associated loci. Several rare variants, including the p.H157Y variant in TREM2, and the p.G186R and p.R274W variants in SHARPIN are associated with risk of AD in East Asians. Extending genetic studies to diverse populations, including East Asians is necessary, which could yield more comprehensive insights into AD, and here we review the recent findings regarding the genetic determinants of AD from an East Asian perspective.

    DOI： 10.1038/s10038-022-01050-z

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    その他リンク： https://www.nature.com/articles/s10038-022-01050-z

  • Genome-wide copy number variation analysis of hepatitis B infection in a Japanese population 査読 国際誌

    Masataka Kikuchi, Kaori Kobayashi, Nao Nishida, Hiromi Sawai, Masaya Sugiyama, Masashi Mizokami, Katsushi Tokunaga, Akihiro Nakaya

    Human Genome Variation   8 ( 1 )   22 - 22   2021年12月

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    担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

    Abstract

    Genome-wide association studies have been performed to identify common genetic variants associated with hepatitis B (HB). However, little is known about copy number variations (CNVs) in HB. In this study, we performed a genome-wide CNV analysis between 1830 healthy controls and 1031 patients with HB infection after quality control. Using signal calling by the Axiom Analysis Suite and CNV detection by PennCNV software, we obtained a total of 4494 CNVs across all individuals. The genes with CNVs that were found only in the HB patients were associated with the immune system, such as antigen processing. A gene-level CNV association test revealed statistically significant CNVs in the contactin 6 (CNTN6) gene. Moreover, we also performed gene-level CNV association tests in disease subgroups, including hepatocellular carcinoma patients, liver cirrhosis patients, and HBV carriers, including asymptomatic carriers and patients with HBV-derived chronic hepatitis. Our findings from germline cells suggested that patient-specific CNVs may be inherent genetic risk factors for HB.

    DOI： 10.1038/s41439-021-00154-w

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    その他リンク： https://www.nature.com/articles/s41439-021-00154-w

  • Synergistic role of retinoic acid signaling and Gata3 during primitive choanae formation 査読 国際誌

    Hiroshi Kurosaka, Jin Mushiake, Mithun Saha, Yanran Wu, Qi Wang, Masataka Kikuchi, Akihiro Nakaya, Sayuri Yamamoto, Toshihiro Inubushi, Satoshi Koga, Lisa L Sandell, Paul A Trainor, Takashi Yamashiro

    Human Molecular Genetics   30 ( 24 )   2383 - 2392   2021年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

    Abstract

    Developmental defects of primitive choanae, an anatomical path to connect the embryonic nasal and oral cavity, result in disorders called choanal atresia (CA), which are associated with many congenital diseases and require immediate clinical intervention after birth. Previous studies revealed that reduced retinoid signaling underlies the etiology of CA. In the present study, by using multiple mouse models which conditionally deleted Rdh10 and Gata3 during embryogenesis, we showed that Gata3 expression is regulated by retinoid signaling during embryonic craniofacial development and plays crucial roles for development of the primitive choanae. Interestingly, Gata3 loss of function is known to cause hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, which exhibits CA as one of the phenotypes in humans. Our model partially phenocopies HDR syndrome with CA, and is thus a useful tool for investigating the molecular and cellular mechanisms of HDR syndrome. We further uncovered critical synergy of Gata3 and retinoid signaling during embryonic development, which will shed light on novel molecular and cellular etiology of congenital defects in primitive choanae formation.

    DOI： 10.1093/hmg/ddab205

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    その他リンク： https://academic.oup.com/hmg/article-pdf/30/24/2383/41389865/ddab205.pdf

  • 認知症のゲノム医療 APOEの遺伝型とミスセンスレアバリアント:臨床応用への可能性

    宮下 哲典, 原 範和, 春日 健作, 菊地 正隆, 尾崎 浩一, 新飯田 俊平, 他田 真理, 柿田 明美, 池内 健

    Dementia Japan   35 ( 4 )   585 - 585   2021年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • ヒト剖検脳による神経疾患横断的なレアバリアント解析 APOE

    宮下 哲典, 他田 真理, 原 範和, 長谷川 舞衣, 月江 珠緒, Lixin Liu, Bin Zhu, Yusran Ady Fitrah, 春日 健作, 菊地 正隆, 柿田 明美, 池内 健

    Dementia Japan   35 ( 4 )   650 - 650   2021年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine 査読

    Masataka Kikuchi, Takanobu Nakazawa, Makoto Kinoshita, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Ryota Hashimoto, Shusuke Numata

    Frontiers in Psychiatry   12   2021年9月

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    担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

    Schizophrenia is a mental illness that involves both genetic and environmental factors. Clozapine, an atypical antipsychotic, is a well-established therapy for treatment-resistant schizophrenia. In this study, we focused on a set of monozygotic twins with treatment-resistant schizophrenia in which one twin effectively responded to clozapine treatment and the other did not. Our previous study generated neurons from induced pluripotent stem (iPS) cells derived from these patients and compared the transcriptome profiles between mock- and clozapine-treated neurons. In this study, we performed genome-wide DNA methylation profiling to investigate the mechanisms underlying gene expression changes. First, we extracted the differentially methylated sites from each twin based on statistical analysis. Then, we combined the DNA methylation profiling with transcriptome profiling from our previous RNA-seq data. Among the genes with altered methylation and expression, we found the different proportions of the genes related to neuronal and synaptic functions between the clozapine responder and non-responder (35.7 and 6.7%, respectively). This trend was observed even when the basal differences between the responder and non-responder was excluded. These results suggest that effective clozapine action may correct the abnormalities of neuronal and synapse functions in schizophrenia via changes in methylation.

    DOI： 10.3389/fpsyt.2021.734606

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  • 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans 査読 国際誌

    Ida E. Sønderby, Dennis van der Meer, Clara Moreau, Tobias Kaufmann, G. Bragi Walters, Maria Ellegaard, Abdel Abdellaoui, David Ames, Katrin Amunts, Micael Andersson, Nicola J. Armstrong, Manon Bernard, Nicholas B. Blackburn, John Blangero, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Robin Bülow, Rune Bøen, Wiepke Cahn, Vince D. Calhoun, Svenja Caspers, Christopher R. K. Ching, Sven Cichon, Simone Ciufolini, Benedicto Crespo-Facorro, Joanne E. Curran, Anders M. Dale, Shareefa Dalvie, Paola Dazzan, Eco J. C. de Geus, Greig I. de Zubicaray, Sonja M. C. de Zwarte, Sylvane Desrivieres, Joanne L. Doherty, Gary Donohoe, Bogdan Draganski, Stefan Ehrlich, Else Eising, Thomas Espeseth, Kim Fejgin, Simon E. Fisher, Tormod Fladby, Oleksandr Frei, Vincent Frouin, Masaki Fukunaga, Thomas Gareau, Tian Ge, David C. Glahn, Hans J. Grabe, Nynke A. Groenewold, Ómar Gústafsson, Jan Haavik, Asta K. Haberg, Jeremy Hall, Ryota Hashimoto, Jayne Y. Hehir-Kwa, Derrek P. Hibar, Manon H. J. Hillegers, Per Hoffmann, Laurena Holleran, Avram J. Holmes, Georg Homuth, Jouke-Jan Hottenga, Hilleke E. Hulshoff Pol, Masashi Ikeda, Neda Jahanshad, Christiane Jockwitz, Stefan Johansson, Erik G. Jönsson, Niklas R. Jørgensen, Masataka Kikuchi, Emma E. M. Knowles, Kuldeep Kumar, Stephanie Le Hellard, Costin Leu, David E. J. Linden, Jingyu Liu, Arvid Lundervold, Astri Johansen Lundervold, Anne M. Maillard, Nicholas G. Martin, Sandra Martin-Brevet, Karen A. Mather, Samuel R. Mathias, Katie L. McMahon, Allan F. McRae, Sarah E. Medland, Andreas Meyer-Lindenberg, Torgeir Moberget, Claudia Modenato, Jennifer Monereo Sánchez, Derek W. Morris, Thomas W. Mühleisen, Robin M. Murray, Jacob Nielsen, Jan E. Nordvik, Lars Nyberg, Loes M. Olde Loohuis, Roel A. Ophoff, Michael J. Owen, Tomas Paus, Zdenka Pausova, Juan M. Peralta, G. Bruce Pike, Carlos Prieto, Erin B. Quinlan, Céline S. Reinbold, Tiago Reis Marques, James J. H. Rucker, Perminder S. Sachdev, Sigrid B. Sando, Peter R. Schofield, Andrew J. Schork, Gunter Schumann, Jean Shin, Elena Shumskaya, Ana I. Silva, Sanjay M. Sisodiya, Vidar M. Steen, Dan J. Stein, Lachlan T. Strike, Ikuo K. Suzuki, Christian K. Tamnes, Alexander Teumer, Anbupalam Thalamuthu, Diana Tordesillas-Gutiérrez, Anne Uhlmann, Magnus O. Ulfarsson, Dennis van ‘t Ent, Marianne B. M, van den Bree, Pierre Vanderhaeghen, Evangelos Vassos, Wei Wen, Katharina Wittfeld, Margaret J. Wright, Ingrid Agartz, Srdjan Djurovic, Lars T. Westlye, Hreinn Stefansson, Kari Stefansson, Sébastien Jacquemont, Paul M. Thompson, Ole A. Andreassen

    Translational Psychiatry   11 ( 1 )   182 - 182   2021年6月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1038/s41398-021-01213-0

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    その他リンク： http://www.nature.com/articles/s41398-021-01213-0

  • Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer’s disease 査読

    Shingo Tsuji, Takeshi Hase, Ayako Yachie-Kinoshita, Taiko Nishino, Samik Ghosh, Masataka Kikuchi, Kazuro Shimokawa, Hiroyuki Aburatani, Hiroaki Kitano, Hiroshi Tanaka

    Alzheimer's Research & Therapy   13 ( 1 )   2021年5月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1186/s13195-021-00826-3

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    その他リンク： https://link.springer.com/article/10.1186/s13195-021-00826-3/fulltext.html

  • Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease 査読 国際誌

    Mitsuru Shinohara†, Masataka Kikuchi†, Miyuki Onishi‐Takeya, Yoshitaka Tashiro, Kaoru Suzuki, Yasuhiro Noda, Shuko Takeda, Masahiro Mukouzono, Seiichi Nagano, Akio Fukumori, Ryuichi Morishita, Akihiro Nakaya, Naoyuki Sato

    FASEB BioAdvances   3 ( 5 )   323 - 333   2021年3月

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    担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1096/fba.2020-00151

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    その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1096/fba.2020-00151

  • Effects of copy number variations on brain structure and risk for psychiatric illness: Large‐scale studies from the ENIGMA working groups on CNVs 査読

    Ida E. Sønderby, Christopher R. K. Ching, Sophia I. Thomopoulos, Dennis Meer, Daqiang Sun, Julio E. Villalon‐Reina, Ingrid Agartz, Katrin Amunts, Celso Arango, Nicola J. Armstrong, Rosa Ayesa‐Arriola, Geor Bakker, Anne S. Bassett, Dorret I. Boomsma, Robin Bülow, Nancy J. Butcher, Vince D. Calhoun, Svenja Caspers, Eva W. C. Chow, Sven Cichon, Simone Ciufolini, Michael C. Craig, Benedicto Crespo‐Facorro, Adam C. Cunningham, Anders M. Dale, Paola Dazzan, Greig I. Zubicaray, Srdjan Djurovic, Joanne L. Doherty, Gary Donohoe, Bogdan Draganski, Courtney A. Durdle, Stefan Ehrlich, Beverly S. Emanuel, Thomas Espeseth, Simon E. Fisher, Tian Ge, David C. Glahn, Hans J. Grabe, Raquel E. Gur, Boris A. Gutman, Jan Haavik, Asta K. Håberg, Laura A. Hansen, Ryota Hashimoto, Derrek P. Hibar, Avram J. Holmes, Jouke‐Jan Hottenga, Hilleke E. Hulshoff Pol, Maria Jalbrzikowski, Emma E. M. Knowles, Leila Kushan, David E. J. Linden, Jingyu Liu, Astri J. Lundervold, Sandra Martin‐Brevet, Kenia Martínez, Karen A. Mather, Samuel R. Mathias, Donna M. McDonald‐McGinn, Allan F. McRae, Sarah E. Medland, Torgeir Moberget, Claudia Modenato, Jennifer Monereo Sánchez, Clara A. Moreau, Thomas W. Mühleisen, Tomas Paus, Zdenka Pausova, Carlos Prieto, Anjanibhargavi Ragothaman, Céline S. Reinbold, Tiago Reis Marques, Gabriela M. Repetto, Alexandre Reymond, David R. Roalf, Borja Rodriguez‐Herreros, James J. Rucker, Perminder S. Sachdev, James E. Schmitt, Peter R. Schofield, Ana I. Silva, Hreinn Stefansson, Dan J. Stein, Christian K. Tamnes, Diana Tordesillas‐Gutiérrez, Magnus O. Ulfarsson, Ariana Vajdi, Dennis Ent, Marianne B. M. Bree, Evangelos Vassos, Javier Vázquez‐Bourgon, Fidel Vila‐Rodriguez, G. Bragi Walters, Wei Wen, Lars T. Westlye, Katharina Wittfeld, Elaine H. Zackai, Kári Stefánsson, Sebastien Jacquemont, Paul M. Thompson, Carrie E. Bearden, Ole A. Andreassen, for the ENIGMA‐CNV Working Group, for the ENIGMA, Deletion Syndrome Working Group

    Human Brain Mapping   2021年2月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1002/hbm.25354

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    その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/hbm.25354

  • Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

    Edith Hofer, Gennady V. Roshchupkin, Hieab H. H. Adams, Maria J. Knol, Honghuang Lin, Shuo Li, Habil Zare, Shahzad Ahmad, Nicola J. Armstrong, Claudia L. Satizabal, Manon Bernard, Joshua C. Bis, Nathan A. Gillespie, Michelle Luciano, Aniket Mishra, Markus Scholz, Alexander Teumer, Rui Xia, Xueqiu Jian, Thomas H. Mosley, Yasaman Saba, Lukas Pirpamer, Stephan Seiler, James T. Becker, Owen Carmichael, Jerome I. Rotter, Bruce M. Psaty, Oscar L. Lopez, Najaf Amin, Sven J. van der Lee, Qiong Yang, Jayandra J. Himali, Pauline Maillard, Alexa S. Beiser, Charles Decarli, Sherif Karama, Lindsay Lewis, Mat Harris, Mark E. Bastin, Ian J. Deary, A. Veronica Witte, Frauke Beyer, Markus Loeffler, Karen A. Mather, Peter R. Schofield, Anbupalam Thalamuthu, John B. Kwok, Margaret J. Wright, David Ames, Julian Trollor, Jiyang Jiang, Henry Brodaty, Wei Wen, Meike W. Vernooij, Albert Hofman, André G. Uitterlinden, Wiro J. Niessen, Katharina Wittfeld, Robin Bülow, Uwe Völker, Zdenka Pausova, G. Bruce Pike, Sophie Maingault, Fabrice Crivello, Christophe Tzourio, Philippe Amouyel, Bernard Mazoyer, Michael C. Neale, Carol E. Franz, Michael J. Lyons, Matthew S. Panizzon, Ole A. Andreassen, Anders M. Dale, Mark Logue, Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro-Conde, Janita Bralten, Derrek P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Jason L. Stein, Paul M. Thompson, Sarah E. Medland, Perminder S. Sachdev, William S. Kremen, Joanna M. Wardlaw, Arno Villringer, Cornelia M. van Duijn, Hans J. Grabe, William T. Longstreth, Myriam Fornage, Tomas Paus, Stephanie Debette, M. Arfan Ikram, Helena Schmidt, Reinhold Schmidt, Sudha Seshadri, Christopher R. K. Ching, Mary Agnes B. McMahon, Natalia Shatokhina, Leo C. P. Zsembik, Ingrid Agartz, Saud Alhusaini, Marcio A. A. Almeida, Dag Alnæs, Inge K. Amlien, Micael Andersson, Tyler Ard, Allison Ashley-Koch, Rachel M. Brouwer, Elizabeth E. L. Buimer, Christian Bürger, Dara M. Cannon, Mallar Chakravarty, Qiang Chen, Joshua W. Cheung, Baptiste Couvy-Duchesne, Shareefa Dalvie, Tânia K. de Araujo, Greig I. de Zubicaray, Sonja M. C. de Zwarte, Anouk Den Braber, Nhat Trung Doan, Katharina Dohm, Stefan Ehrlich, Hannah-Ruth Engelbrecht, Susanne Erk, Chun Chieh Fan, Iryna O. Fedko, Sonya F. Foley, Judith M. Ford, Masaki Fukunaga, Melanie E. Garrett, Tian Ge, Sudheer Giddaluru, Aaron L. Goldman, Nynke A. Groenewold, Dominik Grotegerd, Tiril P. Gurholt, Boris A. Gutman, Narelle K. Hansell, Mathew A. Harris, Marc B. Harrison, Courtney C. Haswell, Michael Hauser, Stefan Herms, Dirk J. Heslenfeld, New Fei Ho, David Hoehn, Per Hoffmann, Laurena Holleran, Martine Hoogman, Jouke-Jan Hottenga, Masashi Ikeda, Deborah Janowitz, Iris E. Jansen, Tianye Jia, Christiane Jockwitz, Ryota Kanai, Dalia Kasperaviciute, Tobias Kaufmann, Sinead Kelly, Masataka Kikuchi, Marieke Klein, Michael Knapp, Annchen R. Knodt, Bernd Krämer, Max Lam, Thomas M. Lancaster, Phil H. Lee, Tristram A. Lett, Iscia Lopes-Cendes, Fabio Macciardi, Andre F. Marquand, Samuel R. Mathias, Tracy R. Melzer, Yuri Milaneschi, Nazanin Mirza-Schreiber, Jose C. V. Moreira, Thomas W. Mühleisen, Bertram Müller-Myhsok, Pablo Najt, Soichiro Nakahara, Kwangsik Nho, Loes M. Olde Loohuis, Dimitri Papadopoulos Orfanos, John F. Pearson, Toni L. Pitcher, Benno Pütz, Anjanibhargavi Ragothaman, Faisal M. Rashid, Ronny Redlich, Céline S. Reinbold, Jonathan Repple, Geneviève Richard, Brandalyn C. Riedel, Shannon L. Risacher, Cristiane S. Rocha, Nina Roth Mota, Lauren Salminen, Arvin Saremi, Andrew J. Saykin, Fenja Schlag, Lianne Schmaal, Rodrigo Secolin, Chin Yang Shapland, Li Shen, Jean Shin, Elena Shumskaya, Ida E. Sønderby, Emma Sprooten, Lachlan T. Strike, Katherine E. Tansey, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Jessica A. Turner, Anne Uhlmann, Costanza Ludovica Vallerga, Dennis van der Meer, Marjolein M. J. van Donkelaar, Liza van Eijk, Theo G. M. van Erp, Neeltje E. M. van Haren, Daan van Rooij, Marie-José van Tol, Jan H. Veldink, Ellen Verhoef, Esther Walton, Mingyuan Wang, Yunpeng Wang, Lars T. Westlye, Christopher D. Whelan, Stephanie H. Witt, Christiane Wolf, Thomas Wolfers, Clarissa L. Yasuda, Dario Zaremba, Zuo Zhang, Alyssa H. Zhu, Marcel P. Zwiers, Eric Artiges, Amelia A. Assareh, Rosa Ayesa-Arriola, Aysenil Belger, Christine L. Brandt, Gregory G. Brown, Sven Cichon, Joanne E. Curran, Gareth E. Davies, Franziska Degenhardt, Bruno Dietsche, Srdjan Djurovic, Colin P. Doherty, Ryan Espiritu, Daniel Garijo, Yolanda Gil, Penny A. Gowland, Robert C. Green, Alexander N. Häusler, Walter Heindel, Beng-Choon Ho, Wolfgang U. Hoffmann, Florian Holsboer, Georg Homuth, Norbert Hosten, Clifford R. Jack, Mihyun Jang, Andreas Jansen, Knut Kolskår, Sanne Koops, Axel Krug, Kelvin O. Lim, Jurjen J. Luykx, Daniel H. Mathalon, Venkata S. Mattay, Sarah Matthews, Jaqueline Mayoral Van Son, Sarah C. McEwen, Ingrid Melle, Derek W. Morris, Bryon A. Mueller, Matthias Nauck, Jan E. Nordvik, Markus M. Nöthen, Daniel S. O’leary, Nils Opel, Marie Laure Paillère Martinot, Adrian Preda, Erin B. Quinlan, Varun Ratnakar, Simone Reppermund, Vidar M. Steen, Fábio R. Torres, Dick J. Veltman, James T. Voyvodic, Robert Whelan, Tonya White, Hidenaga Yamamori, Marina K. M. Alvim, Tim J. Anderson, Alejandro Arias-Vasquez, Bernhard T. Baune, John Blangero, Dorret I. Boomsma, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Juan R. Bustillo, Wiepke Cahn, Vince Calhoun, Xavier Caseras, Svenja Caspers, Gianpiero L. Cavalleri, Fernando Cendes, Aiden Corvin, Benedicto Crespo-Facorro, John C. Dalrymple-Alford, Udo Dannlowski, Eco J. C. de Geus, Norman Delanty, Chantal Depondt, Sylvane Desrivières, Gary Donohoe, Thomas Espeseth, Guillén Fernández, Simon E. Fisher, Herta Flor, Andreas J. Forstner, Clyde Francks, Barbara Franke, David C. Glahn, Randy L. Gollub, Oliver Gruber, Asta K. Håberg, Ahmad R. Hariri, Catharina A. Hartman, Ryota Hashimoto, Andreas Heinz, Manon H. J. Hillegers, Pieter J. Hoekstra, Avram J. Holmes, L. Elliot Hong, William D. Hopkins, Hilleke E. Hulshoff Pol, Terry L. Jernigan, Erik G. Jönsson, René S. Kahn, Martin A. Kennedy, Tilo T. J. Kircher, Peter Kochunov, Stephanie Le Hellard, Nicholas G. Martin, Jean-Luc Martinot, Colm McDonald, Katie L. McMahon, Andreas Meyer-Lindenberg, Rajendra A. Morey, Lars Nyberg, Jaap Oosterlaan, Roel A. Ophoff, Brenda W. J. H. Penninx, Tinca J. C. Polderman, Danielle Posthuma, Marcella Rietschel, Joshua L. Roffman, Laura M. Rowland, Philipp G. Sämann, Gunter Schumann, Kang Sim, Sanjay M. Sisodiya, Jordan W. Smoller, Iris E. Sommer, Beate St Pourcain, Arthur W. Toga, Nic J. A. Van der Wee, Dennis Van’T Ent, Henry Völzke, Henrik Walter, Bernd Weber, Daniel R. Weinberger, Juan Zhou

    Nature Communications   11 ( 1 )   2020年12月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Research  

    Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

    DOI： 10.1038/s41467-020-18367-y

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  • バイオマーカーとリスク遺伝子で再考するアルツハイマー型認知症の臨床診断

    春日 健作, 月江 珠緒, 菊地 正隆, 原 範和, 宮下 哲典, 桑野 良三, 岩坪 威, 池内 健

    臨床神経学   60 ( Suppl. )   S338 - S338   2020年11月

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    記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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  • 日本人コホートJGSCAD、J-ADNI、NCGG、ToMMoにおけるバリアント解析 APOE

    宮下 哲典, 原 範和, 春日 健作, Lixin Liu, 樋口 陽, Bin Zhu, 月江 珠緒, 長谷川 舞衣, Yusran Adyfitrah, 石黒 敬信, 村上 涼太, 菊地 正隆, 中谷 明弘, 尾崎 浩一, 新飯田 俊平, 赤澤 宏平, 桑野 良三, 岩坪 威, 池内 健

    Dementia Japan   34 ( 4 )   521 - 521   2020年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • データドリブンな軽度認知障害のサブタイピングおよびアルツハイマー病発症予測

    菊地 正隆, 小林 香織, 春日 健作, 宮下 哲典, 池内 健, 湯本 英二, 伏見 泰人, 武田 理宏, 真鍋 史朗, 上條 憲一, 松村 泰志

    Dementia Japan   34 ( 4 )   501 - 501   2020年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • ヒト死後脳、ヒト培養細胞におけるAPOEの遺伝子発現解析

    Lixin Liu, 宮下 哲典, 村上 涼太, 原 範和, 菊地 正隆, Bin Zhu, 樋口 陽, Yusran Adyfitrah, 月江 珠緒, 長谷川 舞衣, 春日 健作, 赤津 裕康, 橋詰 良夫, 柿田 明美, 村山 繁雄, 池内 健

    Dementia Japan   34 ( 4 )   521 - 521   2020年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • The genetic architecture of the human cerebral cortex 査読

    Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro-Conde, Janita Bralten, Derrek P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Christopher R. K. Ching, Mary Agnes B. McMahon, Natalia Shatokhina, Leo C. P. Zsembik, Sophia I. Thomopoulos, Alyssa H. Zhu, Lachlan T. Strike, Ingrid Agartz, Saud Alhusaini, Marcio A. A. Almeida, Dag Alnæs, Inge K. Amlien, Micael Andersson, Tyler Ard, Nicola J. Armstrong, Allison Ashley-Koch, Joshua R. Atkins, Manon Bernard, Rachel M. Brouwer, Elizabeth E. L. Buimer, Robin Bülow, Christian Bürger, Dara M. Cannon, Mallar Chakravarty, Qiang Chen, Joshua W. Cheung, Baptiste Couvy-Duchesne, Anders M. Dale, Shareefa Dalvie, Tânia K. de Araujo, Greig I. de Zubicaray, Sonja M. C. de Zwarte, Anouk den Braber, Nhat Trung Doan, Katharina Dohm, Stefan Ehrlich, Hannah-Ruth Engelbrecht, Susanne Erk, Chun Chieh Fan, Iryna O. Fedko, Sonya F. Foley, Judith M. Ford, Masaki Fukunaga, Melanie E. Garrett, Tian Ge, Sudheer Giddaluru, Aaron L. Goldman, Melissa J. Green, Nynke A. Groenewold, Dominik Grotegerd, Tiril P. Gurholt, Boris A. Gutman, Narelle K. Hansell, Mathew A. Harris, Marc B. Harrison, Courtney C. Haswell, Michael Hauser, Stefan Herms, Dirk J. Heslenfeld, New Fei Ho, David Hoehn, Per Hoffmann, Laurena Holleran, Martine Hoogman, Jouke-Jan Hottenga, Masashi Ikeda, Deborah Janowitz, Iris E. Jansen, Tianye Jia, Christiane Jockwitz, Ryota Kanai, Sherif Karama, Dalia Kasperaviciute, Tobias Kaufmann, Sinead Kelly, Masataka Kikuchi, Marieke Klein, Michael Knapp, Annchen R. Knodt, Bernd Krämer, Max Lam, Thomas M. Lancaster, Phil H. Lee, Tristram A. Lett, Lindsay B. Lewis, Iscia Lopes-Cendes, Michelle Luciano, Fabio Macciardi, Andre F. Marquand, Samuel R. Mathias, Tracy R. Melzer, Yuri Milaneschi, Nazanin Mirza-Schreiber, Jose C. V. Moreira, Thomas W. Mühleisen, Bertram Müller-Myhsok, Pablo Najt, Soichiro Nakahara, Kwangsik Nho, Loes M. Olde Loohuis, Dimitri Papadopoulos Orfanos, John F. Pearson, Toni L. Pitcher, Benno Pütz, Yann Quidé, Anjanibhargavi Ragothaman, Faisal M. Rashid, William R. Reay, Ronny Redlich, Céline S. Reinbold, Jonathan Repple, Geneviève Richard, Brandalyn C. Riedel, Shannon L. Risacher, Cristiane S. Rocha, Nina Roth Mota, Lauren Salminen, Arvin Saremi, Andrew J. Saykin, Fenja Schlag, Lianne Schmaal, Peter R. Schofield, Rodrigo Secolin, Chin Yang Shapland, Li Shen, Jean Shin, Elena Shumskaya, Ida E. Sønderby, Emma Sprooten, Katherine E. Tansey, Alexander Teumer, Anbupalam Thalamuthu, Diana Tordesillas-Gutiérrez, Jessica A. Turner, Anne Uhlmann, Costanza Ludovica Vallerga, Dennis van der Meer, Marjolein M. J. van Donkelaar, Liza van Eijk, Theo G. M. van Erp, Neeltje E. M. van Haren, Daan van Rooij, Marie-José van Tol, Jan H. Veldink, Ellen Verhoef, Esther Walton, Mingyuan Wang, Yunpeng Wang, Joanna M. Wardlaw, Wei Wen, Lars T. Westlye, Christopher D. Whelan, Stephanie H. Witt, Katharina Wittfeld, Christiane Wolf, Thomas Wolfers, Jing Qin Wu, Clarissa L. Yasuda, Dario Zaremba, Zuo Zhang, Marcel P. Zwiers, Eric Artiges, Amelia A. Assareh, Rosa Ayesa-Arriola, Aysenil Belger, Christine L. Brandt, Gregory G. Brown, Sven Cichon, Joanne E. Curran, Gareth E. Davies, Franziska Degenhardt, Michelle F. Dennis, Bruno Dietsche, Srdjan Djurovic, Colin P. Doherty, Ryan Espiritu, Daniel Garijo, Yolanda Gil, Penny A. Gowland, Robert C. Green, Alexander N. Häusler, Walter Heindel, Beng-Choon Ho, Wolfgang U. Hoffmann, Florian Holsboer, Georg Homuth, Norbert Hosten, Clifford R. Jack, MiHyun Jang, Andreas Jansen, Nathan A. Kimbrel, Knut Kolskår, Sanne Koops, Axel Krug, Kelvin O. Lim, Jurjen J. Luykx, Daniel H. Mathalon, Karen A. Mather, Venkata S. Mattay, Sarah Matthews, Jaqueline Mayoral Van Son, Sarah C. McEwen, Ingrid Melle, Derek W. Morris, Bryon A. Mueller, Matthias Nauck, Jan E. Nordvik, Markus M. Nöthen, Daniel S. O’Leary, Nils Opel, Marie-Laure Paillère Martinot, G. Bruce Pike, Adrian Preda, Erin B. Quinlan, Paul E. Rasser, Varun Ratnakar, Simone Reppermund, Vidar M. Steen, Paul A. Tooney, Fábio R. Torres, Dick J. Veltman, James T. Voyvodic, Robert Whelan, Tonya White, Hidenaga Yamamori, Hieab H. H. Adams, Joshua C. Bis, Stephanie Debette, Charles Decarli, Myriam Fornage, Vilmundur Gudnason, Edith Hofer, M. Arfan Ikram, Lenore Launer, W. T. Longstreth, Oscar L. Lopez, Bernard Mazoyer, Thomas H. Mosley, Gennady V. Roshchupkin, Claudia L. Satizabal, Reinhold Schmidt, Sudha Seshadri, Qiong Yang, Marina K. M. Alvim, David Ames, Tim J. Anderson, Ole A. Andreassen, Alejandro Arias-Vasquez, Mark E. Bastin, Bernhard T. Baune, Jean C. Beckham, John Blangero, Dorret I. Boomsma, Henry Brodaty, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Juan R. Bustillo, Wiepke Cahn, Murray J. Cairns, Vince Calhoun, Vaughan J. Carr, Xavier Caseras, Svenja Caspers, Gianpiero L. Cavalleri, Fernando Cendes, Aiden Corvin, Benedicto Crespo-Facorro, John C. Dalrymple-Alford, Udo Dannlowski, Eco J. C. de Geus, Ian J. Deary, Norman Delanty, Chantal Depondt, Sylvane Desrivières, Gary Donohoe, Thomas Espeseth, Guillén Fernández, Simon E. Fisher, Herta Flor, Andreas J. Forstner, Clyde Francks, Barbara Franke, David C. Glahn, Randy L. Gollub, Hans J. Grabe, Oliver Gruber, Asta K. Håberg, Ahmad R. Hariri, Catharina A. Hartman, Ryota Hashimoto, Andreas Heinz, Frans A. Henskens, Manon H. J. Hillegers, Pieter J. Hoekstra, Avram J. Holmes, L. Elliot Hong, William D. Hopkins, Hilleke E. Hulshoff Pol, Terry L. Jernigan, Erik G. Jönsson, René S. Kahn, Martin A. Kennedy, Tilo T. J. Kircher, Peter Kochunov, John B. J. Kwok, Stephanie Le Hellard, Carmel M. Loughland, Nicholas G. Martin, Jean-Luc Martinot, Colm McDonald, Katie L. McMahon, Andreas Meyer-Lindenberg, Patricia T. Michie, Rajendra A. Morey, Bryan Mowry, Lars Nyberg, Jaap Oosterlaan, Roel A. Ophoff, Christos Pantelis, Tomas Paus, Zdenka Pausova, Brenda W. J. H. Penninx, Tinca J. C. Polderman, Danielle Posthuma, Marcella Rietschel, Joshua L. Roffman, Laura M. Rowland, Perminder S. Sachdev, Philipp G. Sämann, Ulrich Schall, Gunter Schumann, Rodney J. Scott, Kang Sim, Sanjay M. Sisodiya, Jordan W. Smoller, Iris E. Sommer, Beate St Pourcain, Dan J. Stein, Arthur W. Toga, Julian N. Trollor, Nic J. A. Van der Wee, Dennis van ’t Ent, Henry Völzke, Henrik Walter, Bernd Weber, Daniel R. Weinberger, Margaret J. Wright, Juan Zhou, Jason L. Stein, Paul M. Thompson, Sarah E. Medland

    Science   367 ( 6484 )   2020年3月

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：American Association for the Advancement of Science (AAAS)  

    INTRODUCTION

    The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure.

    RATIONALE

    To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations.

    RESULTS

    We identified 369 nominally genome-wide significant loci ( P &lt; 5 × 10 <sup>−8</sup> ) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 360 loci for which replication data were available, 241 loci influencing surface area and 66 influencing thickness remained significant after replication, with 237 loci passing multiple testing correction ( P &lt; 8.3 × 10 <sup>−10</sup> ; 187 influencing surface area and 50 influencing thickness).

    Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation ( r<sub>G</sub> = −0.32, SE = 0.05, P = 6.5 × 10 <sup>−12</sup> ), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness.

    To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 46 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity.

    We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism.

    CONCLUSION

    This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function.

    Identifying genetic influences on human cortical structure.

    ( A ) Measurement of cortical surface area and thickness from MRI. ( B ) Genomic locations of common genetic variants that influence global and regional cortical structure. ( C ) Our results support the radial unit hypothesis that the expansion of cortical surface area is driven by proliferating neural progenitor cells. ( D ) Cortical surface area shows genetic correlation with psychiatric and cognitive traits. Error bars indicate SE.

    IMAGE CREDITS: (A) K. COURTNEY; (C) M. R. GLASS

    DOI： 10.1126/science.aay6690

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  • Polygenic architecture of human neuroanatomical diversity 査読

    Anne Biton, Nicolas Traut, Jean-Baptiste Poline, Benjamin S. Aribisala, Mark E. Bastin, Robin Bülow, Simon R. Cox, Ian J. Deary, Masaki Fukunaga, Hans J. Grabe, Saskia Hagenaars, Ryota Hashimoto, Masataka Kikuchi, Susana Muñoz Maniega, Matthias Nauck, Natalie A. Royle, Alexander Teumer, Maria, Valdes Hernandez, Uwe Völker, Joanna M, Wardlaw, Katharina Wittfeld, Hidenaga Yamamori, Alzheimer’s Disease, Neuroimaging Initiative, Thomas Bourgeron, Roberto Toro

    Cerebral Cortex   30 ( 4 )   2020年2月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

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  • Disruption of a RAC1-centred protein interaction network is associated with Alzheimer’s disease pathology and causes age-dependent neurodegeneration 査読 国際誌

    Masataka Kikuchi†, Michiko Sekiya†, Norikazu Hara†, Akinori Miyashita, Ryozo Kuwano, Takeshi Ikeuchi, Koichi M. Iijima, Akihiro Nakaya

    Human Molecular Genetics   ddz320 ( 5 )   817 - 833   2020年1月

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    担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1093/hmg/ddz320

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  • Perturbed development of cranial neural crest cells in association with reduced sonic hedgehog signaling underlies the pathogenesis of retinoic-acid-induced cleft palate. 査読 国際誌

    Qi Wang, Hiroshi Kurosaka, Masataka Kikuchi, Akihiro Nakaya, Paul A Trainor, Takashi Yamashiro

    Disease models & mechanisms   12 ( 10 )   2019年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Cleft palate (CP) is one of the most common congenital craniofacial anomalies in humans and can be caused by either single or multiple genetic and environmental factor(s). With respect to environmental factors, excessive intake of vitamin A during early pregnancy is associated with increased incidence of CP in offspring both in humans and in animal models. Vitamin A is metabolized to retinoic acid (RA); however, the pathogenetic mechanism of CP caused by altered RA signaling during early embryogenesis is not fully understood. To investigate the detailed cellular and molecular mechanism of RA-induced CP, we administered all-trans RA to pregnant mice at embryonic day (E)8.5. In the RA-treated group, we observed altered expression of Sox10, which marks cranial neural crest cells (CNCCs). Disruption of Sox10 expression was also observed at E10.5 in the maxillary component of the first branchial arch, which gives rise to secondary palatal shelves. Moreover, we found significant elevation of CNCC apoptosis in RA-treated embryos. RNA-sequencing comparisons of RA-treated embryos compared to controls revealed alterations in Sonic hedgehog (Shh) signaling. More specifically, the expression of Shh and its downstream genes Ptch1 and Gli1 was spatiotemporally downregulated in the developing face of RA-treated embryos. Consistent with these findings, the incidence of CP in association with excessive RA signaling was reduced by administration of the Shh signaling agonist SAG (Smoothened agonist). Altogether, our results uncovered a novel mechanistic association between RA-induced CP with decreased Shh signaling and elevated CNCC apoptosis.

    DOI： 10.1242/dmm.040279

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  • ヒト死後脳におけるAPP・APOEの遺伝子発現解析 査読

    Lixin Liu, 宮下 哲典, 村上 涼太, Bin Zhu, 原 範和, 菊地 正隆, 月江 珠緒, 樋口 陽, 春日 健作, 中谷 明弘, 赤津 裕康, 柿田 明美, 村山 繁雄, 池内 健

    Dementia Japan   33 ( 4 )   519 - 519   2019年10月

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    記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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  • Association of copy number variation of the 15q11.2 (BP1-2) region with cortical and subcortical morphology and cognition 査読

    Dennis van, der Meer, Ida E. Sønderby, Tobias Kaufmann, G. Bragi Walters, Abdel Abdellaoui, David Ames, Katrin Amunts, Micael Andersson, Nicola J. Armstrong, Manon Bernard, Nicholas B. Blackburn, John Blangero, Dorret I Boomsma, Henry Brodaty, Rachel M. Brouwer, Robin Bülow, Wiepke Cahn, Vince D. Calhoun, Svenja Caspers, Gianpiero L. Cavalleri, Christopher, R.K. Ching, Sven Cichon, Simone Ciufolini, Aiden Corvin, Benedicto Crespo-Facorro, Joanne E. Curran, Shareefa Dalvie, Paola Dazzan, Eco J.C. de Geus, Greig I. de Zubicaray, Sonja M.C. de Zwarte, Norman Delanty, Anouk den Braber, Sylvane Desrivieres, Marta Di Forti, Joanne L. Doherty, Gary Donohoe, Stefan Ehrlich, Else Eising, Thomas Espeseth, Simon E. Fisher, Tormod Fladby, Oleksandr Frei, Vincent Frouin, Masaki Fukunaga, Thomas Gareau, David C. Glahn, Hans J. Grabe, Nynke A Groenewold, Ómar Gústafsson, Jan Haavik, Asta K Haberg, Ryota Hashimoto, Jayne Y Hehir-Kwa, Derrek P. Hibar, Manon H.J. Hillegers, Per Hoffmann, Laurena Holleran, Jouke- Jan Hottenga, Hilleke E. Hulshoff Pol, Masashi Ikeda, Sébastien Jacquemont, Neda Jahanshad, Christiane Jockwitz, Stefan Johansson, Erik G. Jönsson, Masataka Kikuchi, Emma E.M. Knowles, John B. Kwok, Stephanie Le Hellard, David E.J. Linden, Jingyu Liu, Arvid Lundervold, Astri J. Lundervold, Nicholas G. Martin, Karen A. Mather, Samuel R. Mathias, Katie L. McMahon, Allan F. McRae, Sarah E. Medland, Torgeir Moberget, Clara Moreau, Derek W. Morris, Thomas W. Mühleisen, Robin M .Murray, Jan E. Nordvik, Lars Nyberg, Loes M, Olde Loohuis, Roel A. Ophoff, Michael J. Owen, Tomas Paus, Zdenka Pausova, Juan M. Peralta, Bruce Pike, Carlos Prieto, Erin Burke Quinlan, Céline S. Reinbold, Tiago Reis Marques, James J.H. Rucker, Perminder S. Sachdev, Sigrid B. Sando, Peter R. Schofield, Andrew J. Schork, Gunter Schumann, Jean Shin, Elena Shumskaya, Ana I. Silva, Sanjay M. Sisodiya, Vidar M. Steen, Dan J. Stein, Lachlan T. Strike, Christian K. Tamnes, Alexander Teumer, Anbupalam Thalamuthu, Diana Tordesillas-Gutiérrez, Anne Uhlmann, Magnús Ö, Úlfarsson, Dennis van, t Ent, Marianne B.M, van den Bree, Evangelos Vassos, Wei Wen, Katharina Wittfeld, Margaret J. Wright, Tetyana Zayats, Anders M. Dale, Srdjan Djurovic, Ingrid Agartz, Lars T Westlye, Hreinn Stefánsson, Kári Stefánsson, Paul M. Thompson, Ole A. Andreassen, for the ENIGMA-CNV working group

    JAMA Psychiatry   77 ( 4 )   420 - 420   2019年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1001/jamapsychiatry.2019.3779

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  • Enhancer variants associated with Alzheimer's disease affect gene expression via chromatin looping. 査読 国際誌

    Masataka Kikuchi, Norikazu Hara, Mai Hasegawa, Akinori Miyashita, Ryozo Kuwano, Takeshi Ikeuchi, Akihiro Nakaya

    BMC medical genomics   12 ( 1 )   128 - 128   2019年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    BACKGROUND: Genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) that may be genetic factors underlying Alzheimer's disease (AD). However, how these AD-associated SNPs (AD SNPs) contribute to the pathogenesis of this disease is poorly understood because most of them are located in non-coding regions, such as introns and intergenic regions. Previous studies reported that some disease-associated SNPs affect regulatory elements including enhancers. We hypothesized that non-coding AD SNPs are located in enhancers and affect gene expression levels via chromatin loops. METHODS: To characterize AD SNPs within non-coding regions, we extracted 406 AD SNPs with GWAS p-values of less than 1.00 × 10- 6 from the GWAS catalog database. Of these, we selected 392 SNPs within non-coding regions. Next, we checked whether those non-coding AD SNPs were located in enhancers that typically regulate gene expression levels using publicly available data for enhancers that were predicted in 127 human tissues or cell types. We sought expression quantitative trait locus (eQTL) genes affected by non-coding AD SNPs within enhancers because enhancers are regulatory elements that influence the gene expression levels. To elucidate how the non-coding AD SNPs within enhancers affect the gene expression levels, we identified chromatin-chromatin interactions by Hi-C experiments. RESULTS: We report the following findings: (1) nearly 30% of non-coding AD SNPs are located in enhancers; (2) eQTL genes affected by non-coding AD SNPs within enhancers are associated with amyloid beta clearance, synaptic transmission, and immune responses; (3) 95% of the AD SNPs located in enhancers co-localize with their eQTL genes in topologically associating domains suggesting that regulation may occur through chromatin higher-order structures; (4) rs1476679 spatially contacts the promoters of eQTL genes via CTCF-CTCF interactions; (5) the effect of other AD SNPs such as rs7364180 is likely to be, at least in part, indirect through regulation of transcription factors that in turn regulate AD associated genes. CONCLUSION: Our results suggest that non-coding AD SNPs may affect the function of enhancers thereby influencing the expression levels of surrounding or distant genes via chromatin loops. This result may explain how some non-coding AD SNPs contribute to AD pathogenesis.

    DOI： 10.1186/s12920-019-0574-8

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  • Retinoic-acid-induced cleft palate is resulted by disturbed Shh signaling 査読

    Qi Wang, Hiroshi Kurosaka, Masataka Kikuchi, Akihiro Nakaya, Paul Trainor, Takashi Yamashiro

    Disease Models & Mechanisms   in press   2019年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

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  • Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia 査読

    Ida E Sønderby, Ómar Gústafsson, Nhat Trung Doan, Derrek P Hibar, Sandra Martin-Brevet, Abdel Abdellaoui, David Ames, Katrin Amunts, Michael Andersson, Nicola J Armstrong, Manon Bernard, Nicholas Blackburn, John Blangero, Dorret I Boomsma, Janita Bralten, Hans-Richard Brattbak, Henry Brodaty, Rachel M Brouwer, Robin Bülow, Vince Calhoun, Svenja Caspers, Gianpiero Cavalleri, Chi-Hua Chen, Sven Cichon, Simone Ciufolini, Aiden Corvin, Benedicto Crespo-Facorro, Joanne E Curran, Anders M Dale, Shareefa Dalvie, Paola Dazzan, Eco J, C de Geus, Greig I. de Zubicaray, Sonja M, C. de Zwarte, Norman Delanty, Anouk den Braber, Sylvane Desrivières, Gary Donohoe, Bogdan Draganski, Stefan Ehrlich, Thomas Espeseth, Simon E Fisher, Barbara Franke, Vincent Frouin, Masaki Fukunaga, Thomas Gareau, David C Glahn, Hans Grabe, Nynke A. Groenewold, Jan Haavik, Asta Håberg, Ryota Hashimoto, Jayne Y Hehir-Kwa, Andreas Heinz, Manon H. J. Hillegers, Per Hoffmann, Laurena Holleran, Jouke-Jan Hottenga, Hilleke E Hulshoff, Masashi Ikeda, Neda Jahanshad, Terry Jernigan, Christiane Jockwitz, Stefan Johansson, Gudrun A Jonsdottir, Erik G Jönsson, Rene Kahn, Tobias Kaufmann, Sinead Kelly, Masataka Kikuchi, Emma E M Knowles, Knut K Kolskår, John B Kwok, Stephanie Le Hellard, Costin Leu, Jingyu Liu, Astri J Lundervold, Arvid Lundervold, Nicholas G. Martin, Karen Mather, Samuel R. Mathias, Mark McCormack, Katie L. McMahon, Allan McRae, Yuri Milaneschi, Clara Moreau, Derek Morris, David Mothersill, Thomas W Mühleisen, Robin Murray, Jan E Nordvik, Lars Nyberg, Loes M, Olde Loohuis, Roel Ophoff, Tomas Paus, Zdenka Pausova, Brenda Penninx, Juan M Peralta, Bruce Pike, Carlos Prieto, Sara Pudas, Erin Quinlan, Daniel S Quintana, Céline S Reinbold, Tiago Reis Marques, Alexandre Reymond, Genevieve Richard, Borja Rodriguez-Herreros, Roberto Roiz-Santiañez, Jarek Rokicki, James Rucker, Perminder Sachdev, Anne-Marthe Sanders, Sigrid B Sando, Lianne Schmaal, Peter R Schofield, Andrew J. Schork, Gunter Schumann, Jean Shin, Elena Shumskaya, Sanjay Sisodiya, Vidar M Steen, Dan J Stein, Stacy Steinberg, Lachlan Strike, Alexander Teumer, Anbu Thalamuthu, Diana Tordesillas-Gutierrez, Jessica Turner, Torill Ueland, Anne Uhlmann, Magnus O. Ulfarsson, Dennis van ’t Ent, Dennis van der Meer, Neeltje E. M. van Haren, Anja Vaskinn, Evangelos Vassos, G. Bragi Walters, Yunpeng Wang, Wei Wen, Christopher D Whelan, Katharina Wittfeld, Margie Wright, Hidenaga Yamamori, Tetyana Zayats, Ingrid Agartz, Lars T Westlye, Sébastien Jacquemont, Srdjan Djurovic, Hreinn Stefánsson, Kári Stefánsson, Paul Thompson, Ole A. Andreassen, for the, European Consortium, for the ENIGMA-CNV working group

    Molecular Psychiatry   25 ( 3 )   584 - 602   2018年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1038/s41380-018-0118-1

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  • Planar cell polarity pathway and development of the human visual cortex

    Jean Shin, Shaojie Ma, Edith Hofer, Yash Patel, Gennady V. Roshchupkin, André M. Sousa, Xueqiu Jian, Rebecca Gottesman, Thomas H. Mosley, Myriam Fornage, Yasaman Saba, Lukas Pirpamer, Reinhold Schmidt, Helena Schmidt, Amaia Carrion-Castillo, Fabrice Crivello, Bernard Mazoyer, Joshua C. Bis, Shuo Li, Qiong Yang, Michelle Luciano, Sherif Karama, Lindsay Lewis, Mark Bastin, Mathew A. Harris, Joanna M. Wardlaw, Ian E. Deary, Markus Scholz, Markus Loeffler, Veronica Witte, Frauke Beyer, Arno Villringer, Nicola J Armstrong, Karen A. Mather, David Ames, Jiyang Jiang, John B Kwok, Peter R. Schofield, Anbupalam Thalamuthu, Julian N. Trollor, Margaret J. Wright, Henry Brodaty, Wei Wen, Perminder S. Sachdev, Natalie Terzikhan, Tavia E. Evans, Hieab H.H.H. Adams, M. Arfan Ikram, Stefan Frenzel, Sandra van der Auwera-Palitschka, Katharina Wittfeld, Robin Bülow, Hans Jörgen Grabe, Christophe Tzourio, Aniket Mishra, Sophie Maingault, Stephanie Debette, Nathan A. Gillespie, Carol E. Franz, William S. Kremen, Linda Ding, Neda Jahanshad, Nenad Sestan, Zdenka Pausova, Sudha Seshadri, Tomas Paus, Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro-Conde, Janita Bralten, Derrek P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Christopher R.K. Ching, Mary Agnes B. McMahon, Natalia Shatokhina, Leo Zsembik, Ingrid Agartz, Saud Alhusaini, Marcio A.A. Almeida, Dag Alnæs, Inge K. Amlien, Micael Andersson, Tyler Ard, Nicola J. Armstrong, Allison Ashley-Koch, Manon Bernard, Rachel M. Brouwer, Elizabeth E.L. Buimer, Robin Bülow, Christian Bürger, Dara M. Cannon, Mallasr Chakravarty, Qiang Chen, Joshua W. Cheung, Baptiste Couvy-Duchesne, Anders M. Dale, Shareefa Dalvie, Tânia K. de Araujo, Greig I. de Zubicaray, Sonja M.C. de Zwarte, Anouk den Braber, Nhat Trung Doan, Katharina Dohm, Stefan Ehrlich, Hannah-Ruth Engelbrecht, Susanne Erk, Chun Chieh Fan, Iryna O. Fedko, Sonya F. Foley, Judith M. Ford, Masaki Fukunaga, Melanie E. Garrett, Tian Ge, Sudheer Giddaluru, Aaron L. Goldman, Nynke A. Groenewold, Dominik Grotegerd, Tiril P. Gurholt, Boris A. Gutman, Narelle K. Hansell, Mathew A. Harris, Marc B. Harrison, Courtney C. Haswell, Michael Hauser, Dirk J. Heslenfeld, David Hoehn, Laurena Holleran, Martine Hoogman, Jouke-Jan Hottenga, Masashi Ikeda, Deborah Janowitz, Iris E. Jansen, Tianye Jia, Christiane Jockwitz, Ryota Kanai, Sherif Karama, Dalia Kasperaviciute, Tobias Kaufmann, Sinead Kelly, Masataka Kikuchi, Marieke Klein, Michael Knapp, Annchen R. Knodt, Bernd Krämer, Thomas M. Lancaster, Phil H. Lee, Tristram A. Lett, Lindsay B. Lewis, Iscia Lopes-Cendes, Michelle Luciano, Fabio Macciardi, Andre F. Marquand, Samuel R. Mathias, Tracy R. Melzer, Yuri Milaneschi, Nazanin Mirza-Schreiber, Jose C.V. Moreira, Thomas W. Mühleisen, Bertram Müller-Myhsok, Pablo Najt, Soichiro Nakahara, Kwangsik Nho, Loes M. Olde Loohuis, Dimitri Papadopoulos Orfanos, John F. Pearson, Toni L. Pitcher, Benno Pütz, Anjanibhargavi Ragothaman, Faisal M. Rashid, Ronny Redlich, Céline S. Reinbold, Jonathan Repple, Geneviève Richard, Brandalyn C. Riedel, Shannon L. Risacher, Cristiane S. Rocha, Nina Roth Mota, Lauren Salminen, Arvin Saremi, Andrew J. Saykin, Fenja Schlag, Lianne Schmaal, Peter R. Schofield, Rodrigo Secolin, Chin Yang Shapland, Li Shen, Jean Shin, Elena Shumskaya, Ida E. Sønderby, Emma Sprooten, Lachlan T. Strike, Katherine E. Tansey, Alexander Teumer, Anbupalam Thalamuthu, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Jessica A. Turner, Anne Uhlmann, Costanza Ludovica Vallerga, Dennis van der Meer, Marjolein M.J. van Donkelaar, Liza van Eijk, Theo G.M. van Erp, Neeltje E.M. van Haren, Daan van Rooij, Marie-José van Tol, Jan H. Veldink, Ellen Verhoef, Esther Walton, Yunpeng Wang, Joanna M. Wardlaw, Wei Wen, Lars T. Westlye, Christopher D. Whelan, Stephanie H. Witt, Katharina Wittfeld, Christiane Wolf, Thomas Wolfers, Clarissa L. Yasuda, Dario Zaremba, Zuo Zhang, Alyssa H. Zhu, Marcel P. Zwiers, Eric Artiges, Amelia A. Assareh, Rosa Ayesa-Arriola, Aysenil Belger, Christine L. Brandt, Gregory G. Brown, Sven Cichon, Joanne E. Curran, Gareth E. Davies, Franziska Degenhardt, Bruno Dietsche, Srdjan Djurovic, Colin P. Doherty, Ryan Espiritu, Daniel Garijo, Yolanda Gil, Penny A. Gowland, Robert C. Green, Alexander N. Häusler, Walter Heindel, Beng-Choon Ho, Wolfgang U. Hoffmann, Florian Holsboer, Georg Homuth, Norbert Hosten, Clifford R. Jack, MiHyun Jang, Andreas Jansen, Knut Kolskår, Sanne Koops, Axel Krug, Kelvin O. Lim, Jurjen J. Luykx, Daniel H. Mathalon, Karen A. Mather, Venkata S. Mattay, Sarah Matthews, Jaqueline Mayoral Van Son, Sarah C. McEwen, Ingrid Melle, Derek W. Morris, Bryon A. Mueller, Matthias Nauck, Jan E. Nordvik, Markus M. Nöthen, Daniel S. O’Leary, Nils Opel, Marie - Laure Paillère Martinot, G. Bruce Pike, Adrian Preda, Erin B. Quinlan, Varun Ratnakar, Simone Reppermund, Vidar M. Steen, Fábio R. Torres, Dick J. Veltman, James T. Voyvodic, Robert Whelan, Tonya White, Hidenaga Yamamori, Marina K.M. Alvim, David Ames, Tim J. Anderson, Ole A. Andreassen, Alejandro Arias-Vasquez, Mark E. Bastin, Bernhard T. Baune, John Blangero, Dorret I. Boomsma, Henry Brodaty, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Juan R. Bustillo, Wiepke Cahn, Vince Calhoun, Xavier Caseras, Svenja Caspers, Gianpiero L. Cavalleri, Fernando Cendes, Aiden Corvin, Benedicto Crespo-Facorro, John C. Dalrymple-Alford, Udo Dannlowski, Eco J.C. de Geus, Ian J. Deary, Norman Delanty, Chantal Depondt, Sylvane Desrivières, Gary Donohoe, Thomas Espeseth, Guillén Fernández, Simon E. Fisher, Herta Flor, Andreas J. Forstner, Clyde Francks, Barbara Franke, David C. Glahn, Randy L. Gollub, Hans J. Grabe, Oliver Gruber, Asta K. Håberg, Ahmad R. Hariri, Catharina A. Hartman, Ryota Hashimoto, Andreas Heinz, Manon H.J. Hillegers, Pieter J. Hoekstra, Avram J. Holmes, L. Elliot Hong, William D. Hopkins, Hilleke E. Hulshoff Pol, Terry L. Jernigan, Erik G. Jönsson, René S. Kahn, Martin A. Kennedy, Tilo T.J. Kircher, Peter Kochunov, John B.J. Kwok, Stephanie Le Hellard, Nicholas G. Martin, Jean - Luc Martinot, Colm McDonald, Katie L. McMahon, Andreas Meyer-Lindenberg, Rajendra A. Morey, Lars Nyberg, Jaap Oosterlaan, Roel A. Ophoff, Tomas Paus, Zdenka Pausova, Brenda W.J.H. Penninx, Tinca J.C. Polderman, Danielle Posthuma, Marcella Rietschel, Joshua L. Roffman, Laura M. Rowland, Perminder S. Sachdev, Philipp G. Sämann, Gunter Schumann, Kang Sim, Sanjay M. Sisodiya, Jordan W. Smoller, Iris E. Sommer, Beate St Pourcain, Dan J. Stein, Arthur W. Toga, Julian N. Trollor, Nic J.A. Van der Wee, Dennis van’t Ent, Henry Völzke, Henrik Walter, Bernd Weber, Daniel R. Weinberger, Margaret J. Wright, Juan Zhou, Jason L. Stein, Paul M. Thompson, Sarah E. Medland

    2018年8月

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  • Genome-wide Association Analysis of Eye Movement Dysfunction in Schizophrenia. 査読 国際誌

    Kikuchi M, Miura K, Morita K, Yamamori H, Fujimoto M, Ikeda M, Yasuda Y, Nakaya A, Hashimoto R

    Scientific reports   8 ( 1 )   12347 - 12347   2018年8月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1038/s41598-018-30646-9

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  • Identification of core gene networks and hub genes associated with progression of non-alcoholic fatty liver disease by RNA sequencing 査読

    Kikuko Hotta, Masataka Kikuchi, Takuya Kitamoto, Aya Kitamoto, Yuji Ogawa, Yasushi Honda, Takaomi Kessoku, Kaori Kobayashi, Masato Yoneda, Kento Imajo, Wataru Tomeno, Akihiro Nakaya, Yutaka Suzuki, Satoru Saito, Atsushi Nakajima

    HEPATOLOGY RESEARCH   47 ( 13 )   1445 - 1458   2017年12月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

    AimNon-alcoholic fatty liver disease (NAFLD) progresses because of the interaction between numerous genes. Thus, we carried out a weighted gene coexpression network analysis to identify core gene networks and key genes associated with NAFLD progression.
    MethodsWe enrolled 39 patients with mild NAFLD (fibrosis stages 0-2) and 21 with advanced NAFLD (fibrosis stages 3-4). Total RNA was extracted from frozen liver biopsies, and sequenced to capture a large dynamic range of expression levels.
    ResultsA total of 1777 genes differentially expressed between mild and advanced NAFLD (q-value &lt;0.05) clustered into four modules. One module was enriched for genes that encode cell surface or extracellular matrix proteins, and are involved in cell adhesion, proliferation, and signaling. This module formed a scale-free network containing four hub genes (PAPLN, LBH, DPYSL3, and JAG1) overexpressed in advanced NAFLD. PAPLN is a component of the extracellular matrix, LBH and DPYSL3 are reported to be tumor suppressors, and JAG1 is tumorigenic. Another module formed a random network, and was enriched for genes that accumulate in the mitochondria. These genes were downregulated in advanced NAFLD, reflecting impaired mitochondrial function. However, the other two modules did not form unambiguous networks. KEGG analysis indicated that 71 differentially expressed genes were involved in pathways in cancer. Strikingly, expression of half of all differentially expressed genes was inversely correlated with methylation of CpG sites (q-value &lt;0.05). Among clinical parameters, serum type IV collagen 7s was most strongly associated with the epigenetic status in NAFLD.
    ConclusionsNewly identified core gene networks suggest that the NAFLD liver undergoes mitochondrial dysfunction and fibrosis, and acquires tumorigenic potential epigenetically. Our data provide novel insights into the pathology and etiology of NAFLD progression, and identify potential targets for diagnosis and treatment.

    DOI： 10.1111/hepr.12877

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  • Bioinformatics analysis of Alzheimer's disease 査読

    Masataka Kikuchi, Akihiro Nakaya

    Brain and Nerve   69 ( 7 )   835 - 842   2017年7月

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    記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

    With the spread of microarray and next-generation sequencing technologies, massive amounts of data can be collected. However, these collections of data require the use of "big data" data-mining techniques to extract the relevant information. These techniques are applied to biological data through bioinformatics studies. By applying these bioinformatics approaches to various omics datasets, the complex pathology of Alzheimer's disease (AD) has been substantially revealed. In this paper, we focus on the genomics-And transcriptomics-based studies, and review previous AD studies using these newer bioinformatics approaches.

    DOI： 10.11477/mf.1416200828

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  • Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells frommonozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine 査読

    Takanobu Nakazawa, Masataka Kikuchi, Mitsuru Ishikawa, Hidenaga Yamamori, Kazuki Nagayasu, Takuya Matsumoto, Michiko Fujimoto, Yuka Yasuda, Mikiya Fujiwara, Shota Okada, Kensuke Matsumura, Atsushi Kasai, Atsuko Hayata-Takano, Norihito Shintani, Shusuke Numata, Kazuhiro Takuma, Wado Akamatsu, Hideyuki Okano, Akihiro Nakaya, Hitoshi Hashimoto, Ryota Hashimoto

    SCHIZOPHRENIA RESEARCH   181   75 - 82   2017年3月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

    Schizophrenia is a chronic psychiatric disorderwith complex genetic and environmental origins. While many antipsychotics have been demonstrated as effective in the treatment of schizophrenia, a substantial number of schizophrenia patients are partially or fully unresponsive to the treatment. Clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia; however, clozapine has rare but serious side-effects. Furthermore, there is inter-individual variability in the drug response to clozapine treatment. Therefore, the identification of the molecular mechanisms underlying the action of clozapine and drug response predictors is imperative. In the present study, we focused on a pair ofmonozygotic twin caseswith treatment-resistant schizophrenia, inwhich one twin responded well to clozapine treatment and the other twin did not. Using induced pluripotent stem (iPS) cell-based technology, we generated neurons from iPS cells derived from these patients and subsequently performed RNA-sequencing to compare the transcriptome profiles of the mock or clozapine-treated neurons. Although, these iPS cells similarly differentiated into neurons, several genes encoding homophilic cell adhesion molecules, such as protocadherin genes, showed differential expression patterns between these two patients. These results, which contribute to the current understanding of the molecular mechanisms of clozapine action, establish a new strategy for the use of monozygotic twin studies in schizophrenia research. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

    DOI： 10.1016/j.schres.2016.10.012

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  • Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia 査読

    Makoto Kinoshita, Shusuke Numata, Atsushi Tajima, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Shinya Watanabe, Hidehiro Umehara, Shinji Shimodera, Takanobu Nakazawa, Masataka Kikuchi, Akihiro Nakaya, Hitoshi Hashimoto, Issei Imoto, Ryota Hashimoto, Tetsuro Ohmori

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   18 ( 3 )   2017年3月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

    Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for "cell substrate adhesion" and "cell matrix adhesion" gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ.

    DOI： 10.3390/ijms18030632

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  • Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease 査読

    Norikazu Hara, Masataka Kikuchi, Akinori Miyashita, Hiroyuki Hatsuta, Yuko Saito, Kensaku Kasuga, Shigeo Murayama, Takeshi Ikeuchi, Ryozo Kuwano

    ACTA NEUROPATHOLOGICA COMMUNICATIONS   5 ( 1 )   10   2017年1月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

    MicroRNAs (miRNAs) are attractive molecules to utilize as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer's disease (AD) because miRNAs are relatively stable in biofluid, including serum or plasma. To determine blood miRNA biomarkers for AD with next-generation sequencing genome-wide, we first surveyed 45 serum samples. These came from 27 AD patients and 18 controls (discovery set) that underwent autopsy within two weeks after their serum sampling and were neuropathologically diagnosed. We found that three miRNAs, hsa-miR-501-3p, hsa-let-7f-5p, and hsa-miR-26b-5p, were significantly deregulated between the AD samples and the controls. The deregulation for hsa-miR-501-3p was further confirmed by quantitative reverse transcription polymerase chain reaction (PCR) in a validation set composed of 36 clinically diagnosed AD patients and 22 age-matched cognitively normal controls with a sensitivity and specificity of 53% and 100%, respectively (area under the curve = 0.82). Serum hsa-miR-501-3p levels were downregulated in AD patients, and its lower levels significantly correlated with lower Mini-Mental State Examination scores. Contrary to its serum levels, we found that hsa-miR-501-3p was remarkably upregulated in the same donors' AD brains obtained at autopsy from the discovery set. The hsa-miR-501-3p overexpression in cultured cells, which mimicked the hsa-miR-501-3p upregulation in the AD brains, induced significant downregulation of 128 genes that overrepresented the Gene Ontology terms, DNA replication, and the mitotic cell cycle. Our results suggest that hsa-miR-501-3p is a novel serum biomarker that presumably corresponds to pathological events occurring in AD brains.

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  • Polygenetic components for schizophrenia, bipolar disorder and rheumatoid arthritis predict risk of schizophrenia 査読

    Kazutaka Ohi, Masataka Kikuchi, Masashi Ikeda, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Haruo Fujino, Kenichiro Miura, Masaki Fukunaga, Akihiro Nakaya, Nakao Iwata, Ryota Hashimoto

    SCHIZOPHRENIA RESEARCH   175 ( 1-3 )   226 - 229   2016年8月

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    記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

    DOI： 10.1016/j.schres.2016.04.009

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  • Network Analysis of a Comprehensive Knowledge Repository Reveals a Dual Role for Ceramide in Alzheimer's Disease 査読

    Satoshi Mizuno, Soichi Ogishima, Kazuyuki Kitatani, Masataka Kikuchi, Hiroshi Tanaka, Nobuo Yaegashi, Jun Nakaya

    PLOS ONE   11 ( 2 )   e0148431   2016年2月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

    Alzheimer's disease (AD) is the most common cause of senile dementia. Many inflammatory factors such as amyloid-beta and pro-inflammatory cytokines are known to contribute to the inflammatory response in the AD brain. Sphingolipids are widely known to have roles in the pathogenesis of inflammatory diseases, where the precise roles for sphingolipids in inflammation-associated pathogenesis of AD are not well understood. Here we performed a network analysis to clarify the importance of sphingolipids and to model relationships among inflammatory factors and sphingolipids in AD. In this study, we have updated sphingolipid signaling and metabolic cascades in a map of AD signaling networks that we named "AlzPathway," a comprehensive knowledge repository of signaling pathways in AD. Our network analysis of the updated AlzPathway indicates that the pathways related to ceramide are one of the primary pathways and that ceramide is one of the important players in the pathogenesis of AD. The results of our analysis suggest the following two prospects about inflammation in AD: (1) ceramide could play important roles in both inflammatory and anti-inflammatory pathways of AD, and (2) several factors such as Sphingomyelinase and Siglec-11 may be associated with ceramide related inflammation and anti-inflammation pathways in AD. In this study, network analysis of comprehensive knowledge repository reveals a dual role for ceramide in AD. This result provides a clue to clarify sphingolipids related inflammatory and anti-inflammatory pathways in AD.

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  • Network-based analysis for uncovering mechanisms underlying Alzheimer's disease 査読

    Masataka Kikuchi, Soichi Ogishima, Satoshi Mizuno, Akinori Miyashita, Ryozo Kuwano, Jun Nakaya, Hiroshi Tanaka

    Systems Biology of Alzheimer's Disease   1303   479 - 491   2015年8月

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    記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer New York  

    Alzheimer's disease (AD) is known to be a multifactorial neurodegenerative disorder, and is one of the main causes of dementia in the elderly. Many studies have demonstrated molecules involved in the pathogenesis of AD, however its underlying mechanisms remain obscure. It may be simplistic to try to explain the disease based on the role of a few genes only. Accumulating new, huge amount of information from e.g. genome, proteome and interactome datasets and new knowledge, we are now able to clarify and characterize diseases essentially as a result of dysfunction of molecular networks. Recent studies have indicated that relevant genes affected in human diseases concentrate in a part of the network, often called as "disease module." In the case of AD, some disease-associated pathways seem different, but some of them are clearly disease-related and coherent. This suggests the existence of a common pathway that negatively drives from healthy state to disease state (i.e., the disease module(s)). Additionally, such disease modules should dynamically change through AD progression. Thus, network-level approaches are indispensable to address unknown mechanisms of AD. In this chapter, we introduce network strategies using gene co-expression and protein interaction networks.

    DOI： 10.1007/978-1-4939-2627-5_29

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  • Alzpathway, an updated map of curated signaling pathways: Towards deciphering Alzheimer's disease pathogenesis 査読

    Soichi Ogishima, Satoshi Mizuno, Masataka Kikuchi, Akinori Miyashita, Ryozo Kuwano, Hiroshi Tanaka, Jun Nakaya

    Systems Biology of Alzheimer's Disease   1303   423 - 432   2015年8月

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    記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer New York  

    Alzheimer's disease (AD) is a complex neurodegenerative disorder in which loss of neurons and synaptic function causes dementia in the elderly. To clarify AD pathogenesis and develop drugs for AD, thousands of studies have elucidated signaling pathways involved. However, knowledge of AD signaling pathways has not been compiled as a pathway map. In this chapter, we introduce the manual construction of a pathway map in AD which we call "AlzPathway", that comprehensively catalogs signaling pathways in the field of AD. We have collected and manually curated over 100 review articles related to AD, and have built the AD pathway map. AlzPathway is currently composed of thousands of molecules and reactions in neurons, brain blood barrier, presynaptic, postsynaptic, astrocyte, and microglial cells, with their cellular localizations. AlzPathway provides a systems-biology platform of comprehensive AD signaling and related pathways which is expected to contribute to clarification of AD pathogenesis and AD drug development.

    DOI： 10.1007/978-1-4939-2627-5_25

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  • Systematic review and meta-analysis of Japanese familial Alzheimer's disease and FTDP-17 査読

    Kensaku Kasuga, Masataka Kikuchi, Takayoshi Tokutake, Akihiro Nakaya, Toshiyuki Tezuka, Tamao Tsukie, Norikazu Hara, Akinori Miyashita, Ryozo Kuwano, Takeshi Ikeuchi

    JOURNAL OF HUMAN GENETICS   60 ( 5 )   281 - 283   2015年5月

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    記述言語：英語   出版者・発行元：NATURE PUBLISHING GROUP  

    Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD pedigrees with mutations have been reported in the Japanese population; however, it remains unclear whether the genetic and clinical features of FAD in the Japanese population differ from those in other populations. To address this issue, we conducted a systematic review and meta-analysis of Japanese FAD and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) by literature search. Using this analysis, we identified 39 different PSEN1 mutations in 140 patients, 5 APP mutations in 35 patients and 16 MAPT mutations in 84 patients. There was no PSEN2 mutation among Japanese patients. The age at onset in Japanese FAD patients with PSEN1 mutations was significantly younger than that in patients with APP mutations. Kaplan-Meier analysis revealed that patients with MAPT mutations showed a shorter survival than patients with PSEN1 or APP mutations. Patients with mutations in different genes exhibit characteristic clinical presentations, suggesting that mutations in causative genes may modify the clinical presentations. By collecting and cataloging genetic and clinical information on Japanese FAD and FTDP-17, we developed an original database designated as Japanese Familial Alzheimer's Disease Database, which is accessible at http://alzdb.bri. niigata-u.ac.jp/.

    DOI： 10.1038/jhg.2015.15

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  • Genes associated with the progression of neurofibrillary tangles in Alzheimer's disease 査読

    A. Miyashita, H. Hatsuta, M. Kikuchi, A. Nakaya, Y. Saito, T. Tsukie, N. Hara, S. Ogishima, N. Kitamura, K. Akazawa, A. Kakita, H. Takahashi, S. Murayama, Y. Ihara, T. Ikeuchi, R. Kuwano

    TRANSLATIONAL PSYCHIATRY   4 ( e396 )   2014年6月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

    The spreading of neurofibrillary tangles (NFTs), intraneuronal aggregates of highly phosphorylated microtubule-associated protein tau, across the human brain is correlated with the cognitive severity of Alzheimer's disease (AD). To identify genes relevant to NFT expansion defined by the Braak stage, we conducted whole-genome exon array analysis with an exploratory sample set consisting of 213 human post-mortem brain tissue specimens from the entorinal, temporal and frontal cortices of 71 brain-donor subjects: Braak NFT stages 0 (N = 13), I-II (N = 20), III-IV (N = 19) and V-VI (N = 19). We identified eight genes, RELN, PTGS2, MYO5C, TRIL, DCHS2, GRB14, NPAS4 and PHYHD1, associated with the Braak stage. The expression levels of three genes, PHYHD1, MYO5C and GRB14, exhibited reproducible association on real-time quantitative PCR analysis. In another sample set, including control subjects (N = 30), and in patients with late-onset AD (N = 37), dementia with Lewy bodies (N = 17) and Parkinson disease (N = 36), the expression levels of two genes, PHYHD1 and MYO5C, were obviously associated with late-onset AD. Protein-protein interaction network analysis with a public database revealed that PHYHD1 interacts with MYO5C via POT1, and PHYHD1 directly interacts with amyloid beta-peptide 42. It is thus likely that functional failure of PHYHD1 and MYO5C could lead to AD development.

    DOI： 10.1038/tp.2014.35

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  • Identification of Unstable Network Modules Reveals Disease Modules Associated with the Progression of Alzheimer's Disease 査読

    Masataka Kikuchi, Soichi Ogishima, Tadashi Miyamoto, Akinori Miyashita, Ryozo Kuwano, Jun Nakaya, Hiroshi Tanaka

    PLOS ONE   8 ( 11 )   e76162   2013年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

    Alzheimer's disease (AD), the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid beta and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs), we identified the PINs expressed in three brain regions: the entorhinal cortex (EC), hippocampus (HIP) and superior frontal gyrus (SFG). Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation-associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system.

    DOI： 10.1371/journal.pone.0076162

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  • A Map of Alzheimer's Disease-Signaling Pathways: A Hope for Drug Target Discovery 査読

    S. Ogishima, S. Mizuno, M. Kikuchi, A. Miyashita, R. Kuwano, H. Tanaka, J. Nakaya

    CLINICAL PHARMACOLOGY & THERAPEUTICS   93 ( 5 )   399 - 401   2013年5月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

    Alzheimer's disease (AD) is a complex neurodegenerative condition, and its drug therapy is challenging. To inform AD drug discovery, we developed the "AlzPathway," a prototype of a comprehensive map of AD-related signaling pathways, from information obtained through studies in the public domain. The AlzPathway provides an integrated platform for systems analyses of AD-signaling pathways and networks.

    DOI： 10.1038/clpt.2013.37

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  • Interactive platform for semantic gene expression analysis of Alzheimer's disease

    Toshiaki Katayama, Masataka Kikuchi, Soichi Ogishima

    CEUR Workshop Proceedings   1114   2013年

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    記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：CEUR-WS  

    In the course of gene expression analysis, it is required to interpret data by referencing knowledge bases of genetics, pathways, diseases and drugs. However, because those external resources are often stored in distributed databases in various formats, it is hard for biomedical scientists to use them in combination. Semantic Web technologies are suitable for integration of those heterogeneous datasets using Resource Description Framework (RDF) and providing a faceted search interface. In this work, we report an application of semantic data integration with faceted search for interactive analysis of gene expression data of Alzheimer's disease. This framework can be easily extended for other biomedical domains.

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  • AlzPathway: a comprehensive map of signaling pathways of Alzheimer's disease 査読

    Satoshi Mizuno, Risa Iijima, Soichi Ogishima, Masataka Kikuchi, Yukiko Matsuoka, Samik Ghosh, Tadashi Miyamoto, Akinori Miyashita, Ryozo Kuwano, Hiroshi Tanaka

    BMC SYSTEMS BIOLOGY   6   52   2012年5月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

    Background: Alzheimer's disease (AD) is the most common cause of dementia among the elderly. To clarify pathogenesis of AD, thousands of reports have been accumulating. However, knowledge of signaling pathways in the field of AD has not been compiled as a database before.
    Description: Here, we have constructed a publicly available pathway map called "AlzPathway" that comprehensively catalogs signaling pathways in the field of AD. We have collected and manually curated over 100 review articles related to AD, and have built an AD pathway map using CellDesigner. AlzPathway is currently composed of 1347 molecules and 1070 reactions in neuron, brain blood barrier, presynaptic, postsynaptic, astrocyte, and microglial cells and their cellular localizations. AlzPathway is available as both the SBML (Systems Biology Markup Language) map for CellDesigner and the high resolution image map. AlzPathway is also available as a web service (online map) based on Payao system, a community-based, collaborative web service platform for pathway model curation, enabling continuous updates by AD researchers.
    Conclusions: AlzPathway is the first comprehensive map of intra, inter and extra cellular AD signaling pathways which can enable mechanistic deciphering of AD pathogenesis. The AlzPathway map is accessible at http://alzpathway.org/.

    DOI： 10.1186/1752-0509-6-52

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  • Dysregulation of iron metabolism in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis 査読

    Satoru Oshiro, Masaki S. Morioka, Masataka Kikuchi

    Advances in Pharmacological Sciences   2011   378278   2011年

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    記述言語：英語  

    Dysregulation of iron metabolism has been observed in patients with neurodegenerative diseases (NDs). Utilization of several importers and exporters for iron transport in brain cells helps maintain iron homeostasis. Dysregulation of iron homeostasis leads to the production of neurotoxic substances and reactive oxygen species, resulting in iron-induced oxidative stress. In Alzheimer's disease (AD) and Parkinson's disease (PD), circumstantial evidence has shown that dysregulation of brain iron homeostasis leads to abnormal iron accumulation. Several genetic studies have revealed mutations in genes associated with increased iron uptake, increased oxidative stress, and an altered inflammatory response in amyotrophic lateral sclerosis (ALS). Here, we review the recent findings on brain iron metabolism in common NDs, such as AD, PD, and ALS. We also summarize the conventional and novel types of iron chelators, which can successfully decrease excess iron accumulation in brain lesions. For example, iron-chelating drugs have neuroprotective effects, preventing neural apoptosis, and activate cellular protective pathways against oxidative stress. Glial cells also protect neurons by secreting antioxidants and antiapoptotic substances. These new findings of experimental and clinical studies may provide a scientific foundation for advances in drug development for NDs. Copyright © 2011 Satoru Oshiro et al.

    DOI： 10.1155/2011/378278

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  • 3P-302 酵母のタンパク質間相互作用ネットワークにおける進化的拘束としてのモジュラー性(生命情報科学・分子進化,第46回日本生物物理学会年会)

    Kikuchi Masataka, Ogishima Soichi, Tanaka Hiroshi

    生物物理   48   S174   2008年

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    記述言語：英語   出版者・発行元：一般社団法人 日本生物物理学会  

    DOI： 10.2142/biophys.48.S174_2

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MISC

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産業財産権

  • ○○○○○の評価装置、評価方法、プログラム、および記録媒体

    菊地正隆, 中谷明弘

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    出願番号：特願2018-0000000 

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  • ○○○○○の評価装置、評価方法、プログラム、および記録媒体

    菊地正隆, 中谷明弘

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    出願番号：特願PCT/JP2018/000000 

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受賞

  • 日本医療情報学会 学術論文賞 最優秀学術論文賞

    2023年11月  

    菊地正隆

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  • JAMI Best Paper Award on APAMI2020

    2020年11月  

    菊地正隆

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  • 中田瑞穂若手研究奨励賞

    2013年7月  

    菊地正隆

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共同研究・競争的資金等の研究

  • アルツハイマー病初期の青斑核ノルアドレナリン神経軸索変性の機序解明とその再生を促す治療標的の同定

    2023年4月 - 2026年3月

    提供機関：AMED: 国立研究開発法人日本医療研究開発機構

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    担当区分：研究分担者 

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  • 認知症疾患コホートを活用したゲノム統合解析による認知症層別化と脳内病態メカニズム解明

    2023年4月 - 2026年3月

    提供機関：AMED: 国立研究開発法人日本医療研究開発機構

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    担当区分：研究分担者 

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  • 日本人剖検脳を用いた脳細胞種別認知症マルチオミックス解析

    研究課題/領域番号：21453679

    2021年8月 - 2024年3月

    提供機関：AMED: 国立研究開発法人日本医療研究開発機構

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    担当区分：研究代表者 

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  • iPS細胞技術とデータ科学を融合した精神疾患横断的な双方向トランスレーショナル研究

    2021年7月 - 2025年3月

    提供機関：AMED: 国立研究開発法人日本医療研究開発機構

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    担当区分：研究分担者 

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  • アルツハイマー病保護因子APOE２多型の作用機序の解明と治療薬開発への応用

    研究課題/領域番号：23K21640

    2021年4月 - 2025年3月

    制度名：科学研究費助成事業

    研究種目：基盤研究(B)

    提供機関：日本学術振興会

    篠原 充, 大塚 礼, 笹栗 弘貴, 齊藤 祐子, 西田 裕紀子, 佐藤 亜希子, 菊地 正隆, 小木曽 昇

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    配分額：17160000円 （ 直接経費：13200000円 、 間接経費：3960000円 ）

    各APOEノックインマウスの加齢化を進め、定期的な活動量変化とともに生存率を評価した。３年近く長生きする場合があり、まだ最終コホートは生存しているが、結果をまとめつつある。それとともに、CRISPR-CAS9で作製した新規遺伝子組み換えマウスのバッククロスをほぼ終え、解析やADマウスモデルとの交配に着手した。長寿遺伝子APOE2の作用を模倣するであろう薬剤について、生体への投与方法の検討を行った。またオミクス解析も進めた。研究のより詳細な内容や結果については論文発表まで公表を控えたい。

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  • アルツハイマー病保護因子APOE２多型の作用機序の解明と治療薬開発への応用

    研究課題/領域番号：21H03391

    2021年4月 - 2025年3月

    制度名：科学研究費助成事業

    研究種目：基盤研究(B)

    提供機関：日本学術振興会

    篠原 充, 佐藤 亜希子, 笹栗 弘貴, 齊藤 祐子, 大塚 礼, 西田 裕紀子, 菊地 正隆, 小木曽 昇

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    担当区分：研究分担者 

    配分額：17160000円 （ 直接経費：13200000円 、 間接経費：3960000円 ）

    各APOEノックインマウスの加齢化を進め、定期的な活動量変化とともに生存率を評価していくとともに、関連する候補分子の測定系や、臨床データ、検体の準備を行った。また新規遺伝子組み換えマウスの作製とともに、長寿遺伝子APOE2の作用を模倣するであろう薬剤の探索や生体への投与方法の検討を行った。研究のより詳細な内容や結果については論文発表まで公表を控えたい。

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  • アルツハイマー病疾患サブタイプを考慮した新規ドラッグリポジショニング法の開発

    研究課題/領域番号：20K15778

    2020年4月 - 2023年3月

    制度名：科学研究費助成事業

    研究種目：若手研究

    提供機関：日本学術振興会

    菊地 正隆

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    担当区分：研究代表者 

    配分額：4160000円 （ 直接経費：3200000円 、 間接経費：960000円 ）

    現在アルツハイマー病 (AD:Alzheimer's Disease) の新薬開発は難航している。効率的な薬剤探索の手法の一つとして既存の薬剤から新たな薬効を見出し別の疾患へ応用するドラッグリポジショニング (DR:Drug Repositioning) が注目されている。中でも公共の遺伝子発現データを用いたデータ駆動型の様々なDR手法が提案されてきた。しかし特定の研究で得られた遺伝子発現データはしばしば再現性が低く、また遺伝子間の関係性も十分に考慮されていない。そこで本研究では独自に収集し解析した約1万件以上の公共のADオミックスデータによるメタアナリシス統計量とADに特化した生体分子ネットワークデータを駆使する。また遺伝子がもつ疾患特徴量や薬剤効果量を遺伝子間の”つながり”を介して周辺に伝播させる新手法の開発を行いADに特化した精度の高いDRを目指す。
    令和3年度は効率的なDRを目指すために疾患のサブタイピングを行った。The Alzheimer's Disease Neuroimaging Initiative (ADNI)から健常者、軽度認知機能障害（MCI）、AD患者に関する髄液バイオマーカーデータや、MRIによる脳体積データ、APOE遺伝子のジェノタイプデータといったマルチモーダルなデータを取得し解析に用いた。このマルチモーダルデータに基づき、異種混合学習法によって決定木を構築した。決定木を構成する葉ノードにおいて、同じ葉ノードに分類された検体群は似た特徴を示すことから1つのサブタイプと考えた。構築した決定木をMCI検体に応用した結果、MCIはいくつかのサブタイプに分類され、健常者に近い検体やADに近い検体群に分類されるとともに、髄液バイオマーカー異常や脳萎縮に関して異なる表現型を示すことがわかった。

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  • 網羅的ゲノム解析とインフォマティクス統合解析による認知症の新規病態解析

    2019年4月 - 2022年3月

    提供機関：AMED: 国立研究開発法人日本医療研究開発機構

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    担当区分：研究分担者 

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  • 剖検脳・罹患部位を用いたマルチオミックス解析による神経変性タウオパチーの病態解明と創薬標的の同定

    2018年10月 - 2021年3月

    提供機関：AMED: 国立研究開発法人日本医療研究開発機構

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    担当区分：研究分担者 

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  • ヒト脳内での２段階にわたるアミロイドβ蓄積の機序の解明

    研究課題/領域番号：18H02725

    2018年4月 - 2021年3月

    制度名：科学研究費助成事業

    研究種目：基盤研究(B)

    提供機関：日本学術振興会

    篠原 充, 赤津 裕康, 菊地 正隆, 齊藤 祐子, 村山 繁雄

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    担当区分：研究分担者 

    配分額：17550000円 （ 直接経費：13500000円 、 間接経費：4050000円 ）

    全長型AβやN末端が短いAβ測定のためのELISA、超高感度ELISAを導入、開発するとともに、疾患段階の異なるヒト剖検脳の複数の脳領域について各種Aβの測定を行った。各種神経炎症マーカー測定とともに、タウの蓄積を精度よく捉えるELISAの開発を行い、各疾患段階、各脳領域でのタウの蓄積を測定し、学術誌に報告した(Shinohara et al., J Neuropathol & Exp Neurol 2021)。さらに網羅的遺伝子発現解析を行い、各種Aβやタウに相関する遺伝子、パスウェイを同定した（未発表）。それらの関与を検証する研究を引き続き行っている。

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  • アルツハイマー病マルチオミックスデータベースの構築

    研究課題/領域番号：17K15049

    2017年4月 - 2020年3月

    制度名：科学研究費助成事業

    研究種目：若手研究(B)

    提供機関：日本学術振興会

    菊地 正隆

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    担当区分：研究代表者 

    配分額：4290000円 （ 直接経費：3300000円 、 間接経費：990000円 ）

    これまでアルツハイマー病(AD)患者死後脳で測定された様々なオミックスデータ(一塩基多型(SNP)、コピー数多型(CNV)、mRNA量、マイクロRNA量など)が解析され報告されてきている。そこで本研究では公開されている入手可能なデータを取得しデータベースを整備するとともに、異なるオミックスデータを組み合わせることで新たなADに関連するパスウェイや遺伝子を同定した。

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  • 認知症臨床ゲノム情報データベース構築に関する開発研究

    2016年9月 - 2019年3月

    提供機関：AMED: 国立研究開発法人日本医療研究開発機構

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    担当区分：連携研究者 

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  • 顎顔面形成不全に関わる遺伝的要因と環境的要因の相互作用解明

    研究課題/領域番号：16K15836

    2016年4月 - 2019年3月

    制度名：科学研究費助成事業

    研究種目：挑戦的萌芽研究

    提供機関：日本学術振興会

    黒坂 寛, 中谷 明弘, 菊地 正隆, 真下 知士

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    担当区分：連携研究者 

    配分額：3380000円 （ 直接経費：2600000円 、 間接経費：780000円 ）

    胎生期における顎顔面の形成は複雑かつ精巧に行われ、その発生過程の不具合は口唇口蓋裂等の顎顔面形成不全の原因となる。同疾患は多因子性疾患であり、胎生期における遺伝的要因と環境的要因に大きな影響を受けて発病する事が知られている。本研究では家族性に頭蓋骨早期癒合症、多数歯アンキローシスを呈する患者や口蓋裂と先天性欠如歯を持つ患者のエキソーム解析を行い新規遺伝子変異を同定した。今後は同新規遺伝子変異の機能解析を細胞株や動物モデルを用いて行い、同疾患の病態をより詳細に解析する予定である。またレチノイン酸シグナルとエタノールの過剰投与の相互作用についても顎顔面形成不全を引き起こす新規メカニズムを解明した。

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  • 疾患に関連するゲノム解析のための統合化された情報処理基盤の構築

    研究課題/領域番号：16K07222

    2016年4月 - 2019年3月

    制度名：科学研究費助成事業

    研究種目：基盤研究(C)

    提供機関：日本学術振興会

    中谷 明弘, 岡崎 敦子, 菊地 正隆, 小林 香織

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    担当区分：研究分担者 

    配分額：4940000円 （ 直接経費：3800000円 、 間接経費：1140000円 ）

    疾患ゲノムの解析に必要となる情報処理システムの開発を進めた。1000ゲノムプロジェクトの日本人DNAサンプルの10検体分（男女各5検体ずつ）の全エクソン配列の解読を行った。同プロジェクトから公開されている日本人DNAサンプルの約100検体分の全エクソン配列の解読の結果と併せてデータベース化した。集団内でゲノム配列中の変異領域がどのように分布しているかを評価するアプリケーションプログラムを開発した。染色体に沿ったゲノムスキャンによって特定の条件を満たす変異が連続する領域をブロック構造として抽出する手法も開発した。これらの開発物を活用して実データの解析を臨床系研究者との共同研究によって実施した。

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  • 治療抵抗性統合失調症に対する客観的診断法及び実用的治療プロトコールの開発

    2016年4月 - 2017年3月

    提供機関：AMED: 国立研究開発法人日本医療研究開発機構

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