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多施設コホートを用いた特発性肺線維症における新規遺伝子多型の同定

Research Project

Project/Area Number 19J21080
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionKyoto University

Principal Investigator

中西 智子 (2020)  京都大学, 医学研究科, 特別研究員(DC1)

Research Fellow 中西 智子 (2019, 2021)  京都大学, 医学研究科, 特別研究員(DC1)
Project Period (FY) 2019-04-25 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2021: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2020: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2019: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywords特発性肺線維症 / 全ゲノムシークエンス
Outline of Research at the Start

特発性肺線維症は、生命予後が約 3-5 年と悪性腫瘍に匹敵する程不良である難治性呼吸器疾患の1つであり、有病率は10万人に1人程度から増加の一途を辿っている。疾患の原因となる遺伝子が同定されているのは全体の2割にとどまり、未だに有効な治療薬がない。我々は特発性肺線維症の患者を対象として全ゲノムシークエンスを含めた遺伝子解析、そしてプロテオームやメタボロームを用いたマルチオミクス解析を行うことで、疾患の原因遺伝子やバイオマーカーの同定を目指す。本研究の最終目標は、特発性肺線維症の分子生物学的機序を紐解くのみならず、創薬などの臨床応用に繋げることである。

Outline of Annual Research Achievements

日本人の多施設コホートにて特発性肺線維症(IPF)を234例集積し、全ゲノムシーケンスを行った。3,137例の健常者コントロールを対照群として、ゲノムワイド関連解析(GWAS)を行った。こちらのみでは有意な変異は同定されなかったが、UKBiobankや他人種由来のGWAS統計量と組み合わせ、9,789人のIPF症例と1,053,676人の対象群のデータを統合したところ、IPFに関連する独立した遺伝子座を29個同定し、うち9個が今回新たに同定された座位であった。その中でTERT遺伝子座のみが人種間で有意な異質性を示した。本研究については現在投稿準備中である。

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (36 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (8 results) Journal Article (17 results) (of which Int'l Joint Research: 16 results,  Peer Reviewed: 17 results,  Open Access: 16 results) Presentation (10 results) (of which Int'l Joint Research: 9 results,  Invited: 2 results) Book (1 results)

  • [Int'l Joint Research] マギル大学/モントリオール大学/シャーブルック大学(カナダ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] ヘルシンキ大学(フィンランド)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] ブロード研究所(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] カロリンスカ研究所/ウプサラ大学(スウェーデン)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] McGill University(カナダ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Imperial Collage London/University of Leicester(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Colorado Denver/University of Colorado Denver(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] McGill University(カナダ)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-192022

    • Author(s)
      Huffman Jennifer E.、Butler-Laporte Guillaume、Khan Atlas、Pairo-Castineira Erola、Drivas Theodore G.、Peloso Gina M.、Nakanishi Tomoko、Ganna Andrea、Verma Anurag、Baillie J. Kenneth、Kiryluk Krzysztof、Richards J. Brent、Zeberg Hugo、COVID-19 Host Genetics Initiative
    • Journal Title

      Nature Genetics

      Volume: 54 Issue: 2 Pages: 125-127

    • DOI

      10.1038/s41588-021-00996-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A first update on mapping the human genetic architecture of COVID-192022

    • Author(s)
      COVID-19 Host Genetics Initiative
    • Journal Title

      Nature

      Volume: 608 Issue: 7921 Pages: E1-E10

    • DOI

      10.1038/s41586-022-04826-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Colocalization of Gene Expression and DNA Methylation with Genetic Risk Variants Supports Functional Roles of <i>MUC5B</i> and <i>DSP</i> in Idiopathic Pulmonary Fibrosis2022

    • Author(s)
      Borie Raphael、Cardwell Jonathan、Konigsberg Iain R.、Moore Camille M.、Zhang Weiming、Sasse Sarah K.、Gally Fabienne、Dobrinskikh Evgenia、Walts Avram、Powers Julie、Brancato Janna、Rojas Mauricio、Wolters Paul J.、Brown Kevin K.、Blackwell Timothy S.、Nakanishi Tomoko、...、Schwartz David A.、Yang Ivana V.
    • Journal Title

      American Journal of Respiratory and Critical Care Medicine

      Volume: 206 Issue: 10 Pages: 1259-1270

    • DOI

      10.1164/rccm.202110-2308oc

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mapping the human genetic architecture of COVID-192022

    • Author(s)
      COVID-19 Host Genetics Initiative
    • Journal Title

      Nature

      Volume: 600(7889) Issue: 7889 Pages: 472-477

    • DOI

      10.1038/s41586-021-03767-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel genes and sex differences in COVID-19 severity2022

    • Author(s)
      Cruz Raquel、Diz-de Almeida Silvia、...、Nakanishi Tomoko、... et al.
    • Journal Title

      Human Molecular Genetics

      Volume: 31 Issue: 22 Pages: 3789-3806

    • DOI

      10.1093/hmg/ddac132

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical, radiological and pathological features of idiopathic and secondary interstitial pneumonia with pleuroparenchymal fibroelastosis in patients undergoing lung transplantation2022

    • Author(s)
      Ikegami Naoya、Nakajima Naoki、Yoshizawa Akihiko、Handa Tomohiro 他
    • Journal Title

      Histopathology

      Volume: 80 Issue: 4 Pages: 665-676

    • DOI

      10.1111/his.14595

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals2022

    • Author(s)
      Butler-Laporte Guillaume、Gonzalez-Kozlova Edgar、Su Chen-Yang、Zhou Sirui、Nakanishi Tomoko、et al.
    • Journal Title

      Clinical Proteomics

      Volume: 19 Issue: 1 Pages: 1-11

    • DOI

      10.1186/s12014-022-09371-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetically increased circulating FUT3 level leads to reduced risk of idiopathic pulmonary fibrosis: a Mendelian randomisation study2021

    • Author(s)
      Nakanishi Tomoko、Cerani Agustin、Forgetta Vincenzo、Zhou Sirui、Allen Richard J.、Leavy Olivia C.、Koido Masaru、Assayag Deborah、Jenkins R. Gisli、Wain Louise V.、Yang Ivana V.、Lathrop G. Mark、Wolters Paul J.、Schwartz David A.、Richards J. Brent
    • Journal Title

      European Respiratory Journal

      Volume: 59 Issue: 2 Pages: 2003979-2003979

    • DOI

      10.1183/13993003.03979-2020

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality2021

    • Author(s)
      Nakanishi Tomoko、Pigazzini Sara、...、Richards J. Brent、Ganna Andrea
    • Journal Title

      Journal of Clinical Investigation

      Volume: 131 Issue: 23 Pages: 1-13

    • DOI

      10.1172/jci152386

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity2021

    • Author(s)
      Zhou Sirui*、Butler-Laporte Guillaume*、Nakanishi Tomoko*、...、Richards J. Brent
    • Journal Title

      Nature Medicine

      Volume: 27 Issue: 4 Pages: 659-667

    • DOI

      10.1038/s41591-021-01281-1

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-192021

    • Author(s)
      Povysil Gundula、Butler-Laporte Guillaume、Shang Ning、Wang Chen、Khan Atlas、Alaamery Manal、Nakanishi Tomoko、et al.
    • Journal Title

      Journal of Clinical Investigation

      Volume: 131 Issue: 14 Pages: 1-7

    • DOI

      10.1172/jci147834

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality2021

    • Author(s)
      Brunet-Ratnasingham Elsa、Anand Sai Priya、...、Nakanishi Tomoko、et al.
    • Journal Title

      Science Advances

      Volume: 7 Issue: 48 Pages: 1-16

    • DOI

      10.1126/sciadv.abj5629

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals2021

    • Author(s)
      Kosmicki Jack A.、Horowitz Julie E.、...、Nakansihi Tomoko、et al.
    • Journal Title

      The American Journal of Human Genetics

      Volume: 108 Issue: 7 Pages: 1350-1355

    • DOI

      10.1016/j.ajhg.2021.05.017

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic Determinants of Antibody-Mediated Immune Responses to Infectious Diseases Agents: A Genome-Wide and HLA Association Study2020

    • Author(s)
      Butler-Laporte Guillaume、Kreuzer Devin、Nakanishi Tomoko、Harroud Adil、Forgetta Vincenzo、Richards J Brent
    • Journal Title

      Open Forum Infectious Diseases

      Volume: 7 Issue: 11

    • DOI

      10.1093/ofid/ofaa450

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genomewide Association Study of Severe Covid-19 with Respiratory Failure2020

    • Author(s)
      The Severe Covid-19 GWAS Group
    • Journal Title

      New England Journal of Medicine

      Volume: 383 Issue: 16 Pages: 1522-1534

    • DOI

      10.1056/nejmoa2020283

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The undiagnosed disease burden associated with alpha-1 antitrypsin deficiency genotypes2020

    • Author(s)
      Nakanishi Tomoko、Forgetta Vincenzo、Handa Tomohiro、Hirai Toyohiro、Mooser Vincent、Lathrop G. Mark、Cookson William O.C.M.、Richards J. Brent
    • Journal Title

      European Respiratory Journal

      Volume: 56 Issue: 6 Pages: 2001441-2001441

    • DOI

      10.1183/13993003.01441-2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The effect of angiotensin-converting enzyme levels on COVID-19 susceptibility and severity: a Mendelian randomization study2020

    • Author(s)
      Butler-Laporte Guillaume*、Nakanishi Tomoko*、Mooser Vincent、Renieri Alessandra、Amitrano Sara、Zhou Sirui、Chen Yiheng、Forgetta Vincenzo、Richards J Brent
    • Journal Title

      International Journal of Epidemiology

      Volume: 50 Issue: 1 Pages: 75-86

    • DOI

      10.1093/ije/dyaa229

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 線維化性間質性肺疾患における遺伝的背景の人種及び疾患横断的検討2022

    • Author(s)
      中西智子
    • Organizer
      第62回日本呼吸器学会学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality2021

    • Author(s)
      Nakanishi T, Cordioli M, Richards JB, Ganna A
    • Organizer
      Workshop: Research Response to COVID-19 in the Nordic Countries. Nordic Society of Human Genetics and Precision Medicine
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genetically increased circulating FUT3 level is associated with reduced risk of Idiopathic Pulmonary Fibrosis: a Mendelian Randomization Study.2021

    • Author(s)
      Nakanishi T, Cerani A, Forgetta V, Zhou S, Allen RJ, Leavy OC, Koido M, Assayag D, Jenkins RG, Wain LV, Yang IV, Lathrop GM, Wolters PJ, Schwartz DA, Richards JB.
    • Organizer
      The 2021 Annual Meeting of the American Society of Human Genetics.
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A genetic landscape of Pulmonary Fibrosis in Japanese population. ~ A Preliminary Study ~2021

    • Author(s)
      Nakanishi T, Kamatani Y, Nagasaki M, Handa T, Hirai T, and Matsuda F
    • Organizer
      1st International Symposium of CCII -Bioinformatics and its application to cancer and other diseases
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality2021

    • Author(s)
      Nakanishi T
    • Organizer
      The meeting of the COVID-19 Host Genetics Initiative
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The Undiagnosed Disease Burden Associated with Alpha-1 Antitrypsin Deficiency.2020

    • Author(s)
      Nakanishi T, Forgetta V, Handa T, Hirai T, Mooser V, Lathrop GM, Cookson WOCM, and Richards JB.
    • Organizer
      American Thoracic Society International Conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Undiagnosed Disease Burden Associated with Alpha-1 Antitrypsin Deficiency.2020

    • Author(s)
      Nakanishi T, Forgetta V, Handa T, Hirai T, Mooser V, Lathrop GM, Cookson WOCM, and Richards JB.
    • Organizer
      20th American Society of Human Genetics
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Undiagnosed Disease Burden Associated with Alpha-1 Antitrypsin Deficiency.2020

    • Author(s)
      Nakanishi T, Forgetta V, Handa T, Hirai T, Mooser V, Lathrop GM, Cookson WOCM, and Richards JB.
    • Organizer
      20th Annual McGill Biomedical Graduate Conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Deep clinical phenotyping to assess the effect of GWAS loci on COVID-19 severity.2020

    • Author(s)
      Nakanishi T
    • Organizer
      International Discussion Group on COVID Related Activities
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A genetic landscape of Pulmonary Fibrosis in Japanese population. - A Preliminary Study -2019

    • Author(s)
      Nakanishi T, Kamatani Y, Handa T, Hirai T, Matsuda F.
    • Organizer
      8th Canadian Human and Statistical Genetics Meeting, Montebello, Canada, Jun 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Book] α1-アンチトリプシン欠乏症 診療の手引き2021[第2版]2021

    • Author(s)
      佐藤 晋、佐藤 匡、瀬山 邦明、中西 智子、巽 浩一郎、平井 豊博
    • Total Pages
      23
    • Publisher
      厚生労働科学研究費補助金(難治性疾患政策研究事業)/難治性呼吸器疾患・肺高血圧症に関する調査研究班
    • Related Report
      2021 Annual Research Report

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Published: 2019-05-29   Modified: 2024-12-25  

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