Multi-omics database for Alzheimer's disease

• Project/Area Number: 17K15049
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: System genome science
• Research Institution: Osaka University
• Principal Investigator: Kikuchi Masataka 大阪大学, 医学系研究科, 特任講師(常勤) (90722538)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アルツハイマー病 / データベース / 遺伝子ネットワーク / マルチオミックス / 生体生命情報学 / 脳神経疾患

Outline of Final Research Achievements

The various omics data that were measured in postmortem brains of the patients with Alzheimer's disease have been analyzed and reported. We obtained publicly available data and constructed a database. Furthermore, we identified AD-related pathways and genes by combining the various omics data.

Academic Significance and Societal Importance of the Research Achievements

現在ある公開データベースの多くは解析機器から出力された一次データが保管されているリポジトリとしての役割が強く、蓄積されたデータの応用に至っているとは言い難い。そのような観点から、蓄積されたデータを再利用し、解析ができるデータベースを開発することの意義は大きい。さらに患者死後脳で測定された様々なオミックスデータを解析することでADに関連する新たな分子パスウェイを推定することができた。本研究で構築したデータベースを今後さらに強化し、研究者等に幅広く公開することでAD研究の推進に役立つと考えられる。

Research Products

• [Journal Article] Polygenic Architecture of Human Neuroanatomical Diversity (2020)
  • Author(s): Biton Anne, Kikuchi Masataka (13 of 25 authors), Toro Roberto
  • Journal Title: Cerebral Cortex Volume: 30 Issue: 4 Pages: 2307-2320
  • DOI: 10.1093/cercor/bhz241
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The genetic architecture of the human cerebral cortex (2020)
  • Author(s): Grasby L Katrina, Kikuchi Masataka (79 of 348 authors), Medland E Sarah
  • Journal Title: Science Volume: 367
  • DOI: 10.1101/399402
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Disruption of a RAC1-centred network is associated with Alzheimer's disease pathology and causes age-dependent neurodegeneration. (2020)
  • Author(s): Masataka Kikuchi, Michiko Sekiya, Norikazu Hara, Akinori Miyashita, Ryozo Kuwano, Takeshi Ikeuchi, Koichi M Iijima, Akihiro Nakaya
  • Journal Title: Human Molecular Genetics Volume: 29 Issue: 5 Pages: 817-833
  • DOI: 10.1093/hmg/ddz320
  • Peer Reviewed / Open Access
• [Journal Article] Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition (2020)
  • Author(s): Writing Committee for the ENIGMA-CNV Working Group、van der Meer Dennis、S?nderby Ida E.、Kaufmann Tobias、Walters G. Bragi、...、Fukunaga Masaki、....、Hashimoto Ryota、...、Dale Anders M.、Djurovic Srdjan、Agartz Ingrid、Westlye Lars T.、Stefansson Hreinn、Stefansson K、Thompson Paul M.、Andreassen Ole A.
  • Journal Title: JAMA Psychiatry Volume: 77 Issue: 4 Pages: 420-420
  • DOI: 10.1001/jamapsychiatry.2019.3779
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 特集 認知症と遺伝 アルツハイマー病リスク因子としてのアポリポ蛋白E4 (2019)
  • Author(s): 菊地 正隆、中谷 明弘
  • Journal Title: BRAIN and NERVE Volume: 71 Issue: 10 Pages: 1053-1060
  • DOI: 10.11477/mf.1416201404
  • ISSN: 1344-8129, 1881-6096
  • Year and Date: 2019-10-01
• [Journal Article] Perturbed development of cranial neural crest cells in association with reduced sonic hedgehog signaling underlies the pathogenesis of retinoic-acid-induced cleft palate (2019)
  • Author(s): Wang Qi、Kurosaka Hiroshi、Kikuchi Masataka、Nakaya Akihiro、Trainor Paul A.、Yamashiro Takashi
  • Journal Title: Disease Models & Mechanisms Volume: 12 Issue: 10 Pages: 040279-040279
  • DOI: 10.1242/dmm.040279
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhancer variants associated with Alzheimer’s disease affect gene expression via chromatin looping (2019)
  • Author(s): Kikuchi Masataka、Hara Norikazu、Hasegawa Mai、Miyashita Akinori、Kuwano Ryozo、Ikeuchi Takeshi、Nakaya Akihiro
  • Journal Title: BMC Medical Genomics Volume: 12 Issue: 1 Pages: 128-128
  • DOI: 10.1186/s12920-019-0574-8
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide Association Analysis of Eye Movement Dysfunction in Schizophrenia. (2018)
  • Author(s): Kikuchi M, Miura K, Morita K, Yamamori H, Fujimoto M, Ikeda M, Yasuda Y, Nakaya A, uHashimoto R.
  • Journal Title: Sci Rep Volume: 8(1) Issue: 1 Pages: 12347-12347
  • DOI: 10.1038/s41598-018-30646-9
  • NAID: 120006549303
  • Peer Reviewed / Open Access
• [Journal Article] 増大特集 あしたのアルツハイマー病治療 アルツハイマー病のバイオインフォマティクス解析 (2017)
  • Author(s): 菊地 正隆、中谷 明弘
  • Journal Title: BRAIN and NERVE Volume: 69 Issue: 7 Pages: 835-842
  • DOI: 10.11477/mf.1416200828
  • ISSN: 1344-8129, 1881-6096
  • Year and Date: 2017-07-01
• [Journal Article] アルツハイマー病の遺伝学的リスク (2017)
  • Author(s): 宮下哲典、原範和、春日健作、菊地正隆、中谷明弘、池内健
  • Journal Title: 老年精神医学 Volume: 28 Pages: 754-764
• [Journal Article] バイオインフォマティクスを活用したアルツハイマー病病態解析 (2017)
  • Author(s): 菊地 正隆、中谷 明弘
  • Journal Title: 分子精神医学 Volume: 17 Pages: 71-77
• [Presentation] Polygenic analysis of Alzheimer’s disease in a Japanese population (2020)
  • Author(s): Masataka Kikuchi
  • Organizer: Asian Forum on Alzheimer's Disease
  • Int'l Joint Research
• [Presentation] 日本人集団におけるアルツハイマー病ポリジェニック解析 (2019)
  • Author(s): 菊地正隆,宮下哲典,原範和,重水大智,尾崎浩一,新飯田俊平,池内健,中谷明弘
  • Organizer: 日本認知症学会学術集会
• [Presentation] ヒト死後脳におけるAPP・APOEの遺伝子発現解析 (2019)
  • Author(s): LIU Lixin,宮下哲典,村上涼太,ZHU Bin,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
  • Organizer: 日本認知症学会学術集会
• [Presentation] 日本人におけるAPOEのコモン・レアバリアント解析 (2019)
  • Author(s): 宮下哲典,原範和,春日健作,LIU Lixin,樋口陽,ZHU Bin,月江珠緒,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,桑野良三,岩坪威,岩坪威,池内健
  • Organizer: 日本認知症学会学術集会
• [Presentation] Polygenic analysis of Alzheimer’s disease in a Japanese population (2019)
  • Author(s): Masataka Kikuchi, Akinori Miyashita, Norikazu Hara, Daichi Shigemizu, Kouichi Ozaki, Shumpei Niida, Takechi Ikeuchi, Akihiro Nakaya
  • Organizer: The 13th International Workshop on Advanced Genomics
  • Int'l Joint Research
• [Presentation] Polygenic analyses of Alzheimer's disease in Japanese population (2019)
  • Author(s): Masataka Kikuchi, Akinori Miyashita, Takechi Ikeuchi, Akihiro Nakaya
  • Organizer: Alzheimer's Association International Conference
  • Int'l Joint Research
• [Presentation] ポリジェニックハザードスコアを用いたアルツハイマー病発症年齢解析 (2018)
  • Author(s): 菊地正隆, 宮下哲典, 池内健, 中谷明弘
  • Organizer: 日本認知症学会学術集会
• [Presentation] APOE遺伝型はAPPの遺伝子発現量に影響を及ぼすか?:ヒト死後脳における検証 (2018)
  • Author(s): 村上涼太, 朱斌, 原範和, 菊地正隆, 月江珠緒, 春日健作, 宮下哲典, 中谷明弘, 赤津裕康, 柿田明美, 村山繁雄, 池内健
  • Organizer: 日本認知症学会学術集会
• [Presentation] アルツハイマー病の原因遺伝子と感受性遺伝子:我々の取り組みと国内外の最新情報 (2018)
  • Author(s): 宮下哲典, 原範和, 菊地正隆, 月江珠緒, 春日健作, 中谷明弘, 池内健
  • Organizer: 日本認知症学会学術集会
• [Presentation] Enhancer variants associated with Alzheimer's disease affect gene expression via chromatin looping (2018)
  • Author(s): Masataka Kikuchi
  • Organizer: The Asian Forum on Alzheimer’s and Dementia
  • Int'l Joint Research / Invited
• [Remarks] ADMIX database
  • URL: http://www.alzdb.org/admix/gene_submit.html