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2015 Fiscal Year Annual Research Report

遺伝統計学とビッグデータの邂逅がもたらす新たながんゲノム創薬

Planned Research

Project AreaConquering cancer through neo-dimensional systems understanding
Project/Area Number 15H05911
Research InstitutionTokyo Medical and Dental University

Principal Investigator

岡田 随象  東京医科歯科大学, 大学院医歯学総合研究科, テニュアトラック講師 (70727411)

Co-Investigator(Kenkyū-buntansha) 鎌谷 洋一郎  国立研究開発法人理化学研究所, 統合生命医科学研究センター, チームリーダー (00720880)
藤本 明洋  国立研究開発法人理化学研究所, 統合生命医科学研究センター, 副チームリーダー (30525853)
浦山 ケビン  東京医科歯科大学, 大学院医歯学総合研究科, テニュアトラック講師 (60726850)
川上 英良  国立研究開発法人理化学研究所, 統合生命医科学研究センター, 特別研究員 (30725338)
Project Period (FY) 2015-06-29 – 2020-03-31
Keywords遺伝統計学 / バイオインフォマティクス / マイクロRNA / バイオマーカー
Outline of Annual Research Achievements

近年のヒトゲノム解析技術の革新に伴い、がんを含むヒト疾患感受性遺伝子や遺伝子発現プロファイルが大容量で得られる時代となった一方、ビッグデータを横断的に統合する学問分野の開拓や、ゲノム情報に基づく新規創薬手法の開発は遅れが指摘されている。本研究計画は、大規模ヒト疾患ゲノム解析情報を活用した遺伝統計解析およびバイオインフォマティクス解析を通じた、新たながん疾患病態ネットワークの解明を目的とする。本年度の研究においては、大規模疾患ゲノム解析の成果に基づきマイクロRNAのインシリコ・スクリーニングを行う遺伝統計解析手法(MIGWAS:miRNA target gene enrichment analysis in GWAS)を開発した。MIGWASを18形質(身長、肥満、血液検査値、生化学検査値、生活習慣病、精神疾患、臓器疾患、免疫関連疾患、等)、175万人以上を対象とした既存のゲノムビッグデータ解析結果に適用した結果、関節リウマチを含むヒト形質の遺伝的背景にマイクロRNAが寄与していることを明らかにした。自己免疫疾患である関節リウマチにおいては新規疾患感受性遺伝子PADI2と、PADI2の翻訳を制御するマイクロRNA miR-4728-5pの同定に成功している。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

MIGWASを開発し、実際の大規模ヒト疾患ゲノム解析結果への適用を通じてその妥当性を実証できたため。

Strategy for Future Research Activity

がん疾患を対象に、MIGWASの適用とがんバイオマーカーの同定を進めていく。

  • Research Products

    (11 results)

All 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 8 results,  Acknowledgement Compliant: 3 results,  Open Access: 2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] Broad Institute/Harvard Medical School(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      Broad Institute/Harvard Medical School
  • [Int'l Joint Research] Sanger Institute/Cambridge University(英国)

    • Country Name
      UNITED KINGDOM
    • Counterpart Institution
      Sanger Institute/Cambridge University
  • [Journal Article] Significant impact of miRNA-target gene networks on genetics of human complex traits2016

    • Author(s)
      Okada Y, Muramatsu T, Suita N, Kanai M, Kawakami E et al.
    • Journal Title

      Sci Rep

      Volume: 6 Pages: 22223

    • DOI

      10.1038/srep22223.

    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] meta-analysis of genome-wide association studies in the Japanese population identifies 7 novel loci associated with type 2 diabetes2016

    • Author(s)
      Imamura M, Takahashi A, Yamauchi T, Hara K, Yasuda K, ... Okada Y et al.
    • Journal Title

      Nat Commun

      Volume: 7 Pages: 10531

    • DOI

      10.1038/ncomms10531

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry2016

    • Author(s)
      Sun C, Molineros JE, Looger LL, Zhou XJ, Kim K, Okada Y et al.
    • Journal Title

      Nat Genet

      Volume: 48 Pages: 323-330

    • DOI

      10.1038/ng.3496

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ethnically shared and heterogeneous impacts of molecular pathways suggested by the genome-wide meta-analysis of rheumatoid arthritis.2016

    • Author(s)
      Okada Y, Raj T, Yamamoto K
    • Journal Title

      Rheumatology (Oxford)

      Volume: 55 Pages: 186-189

    • DOI

      10.1093/rheumatology/kev314.

    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese2015

    • Author(s)
      Okada Y, Momozawa Y, Ashikawa K, Kanai M, Matsuda K et al.
    • Journal Title

      Nat Genet

      Volume: 47 Pages: 798-802

    • DOI

      10.1186/s13075-015-0623-4

    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Partitioning heritability by functional annotation using genome-wide association summary statistics2015

    • Author(s)
      Finucane HK, Bulik-Sullivan B, Gusev A, Trynka G, Reshef Y, ... Okada Y et al.
    • Journal Title

      Nat Genet

      Volume: 47 Pages: 1228-1235

    • DOI

      10.1038/ng.3404

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases.2015

    • Author(s)
      Lenz TL, Deutsch AJ, Han B, Hu X, Okada Y et al.
    • Journal Title

      Nat Genet

      Volume: 47 Pages: 1085-1090

    • DOI

      10.1038/ng.3379

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Directional dominance on stature and cognition in diverse human populations2015

    • Author(s)
      Joshi PK, Esko T, Mattsson H, Eklund N, Gandin I, ... Okada Y et al.
    • Journal Title

      Nature

      Volume: 523 Pages: 459-462

    • DOI

      10.1038/nature14618

    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Identification of the risk HLA variants of Graves' disease by applying the HLA imputation method to large scale Japanese genome-wide association study data2015

    • Author(s)
      Okada Y, Momozawa Y, Ashikawa K, Kanai M, Matsuda K et al.
    • Organizer
      17th Asia Pacific League of Associations for Rheumatology Congress
    • Place of Presentation
      Chennai, India
    • Year and Date
      2015-09-05 – 2015-09-05
    • Int'l Joint Research

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Published: 2017-01-06   Modified: 2022-10-18  

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