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Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis

Author

Listed:
  • Younghun Han

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Jinyoung Byun

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

  • Catherine Zhu

    (Baylor College of Medicine)

  • Ryan Sun

    (University of Texas, M.D. Anderson Cancer Center)

  • Julia Y. Roh

    (Ochsner Health)

  • Heather J. Cordell

    (Newcastle University)

  • Hyun-Sung Lee

    (Baylor College of Medicine)

  • Vikram R. Shaw

    (Baylor College of Medicine)

  • Sung Wook Kang

    (Baylor College of Medicine)

  • Javad Razjouyan

    (Michael E. DeBakey VA Medical Center
    VA Office of Research and Development
    Baylor College of Medicine
    Michael E. DeBakey VA Medical Center)

  • Matthew A. Cooley

    (Mayo Clinic)

  • Manal M. Hassan

    (The University of Texas MD Anderson Cancer Center)

  • Katherine A. Siminovitch

    (University of Toronto
    Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute and Toronto General Research Institute, Toronto)

  • Trine Folseraas

    (Oslo University Hospital Rikshospitalet)

  • David Ellinghaus

    (Christian-Albrechts-University of Kiel)

  • Annika Bergquist

    (Karolinska Institutet, Karolinska University Hospital)

  • Simon M. Rushbrook

    (Norfolk and Norwich University Hospital
    University of East Anglia)

  • Andre Franke

    (Christian-Albrechts-University of Kiel)

  • Tom H. Karlsen

    (Oslo University Hospital Rikshospitalet and University of Oslo)

  • Konstantinos N. Lazaridis

    (Mayo Clinic)

  • Katherine A. McGlynn

    (National Cancer Institute)

  • Lewis R. Roberts

    (Oslo University Hospital Rikshospitalet and University of Oslo)

  • Christopher I. Amos

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

Abstract

Primary sclerosing cholangitis (PSC) is a rare autoimmune bile duct disease that is strongly associated with immune-mediated disorders. In this study, we implemented multitrait joint analyses to genome-wide association summary statistics of PSC and numerous clinical and epidemiological traits to estimate the genetic contribution of each trait and genetic correlations between traits and to identify new lead PSC risk-associated loci. We identified seven new loci that have not been previously reported and one new independent lead variant in the previously reported locus. Functional annotation and fine-mapping nominated several potential susceptibility genes such as MANBA and IRF5. Network-based in silico drug efficacy screening provided candidate agents for further study of pharmacological effect in PSC.

Suggested Citation

  • Younghun Han & Jinyoung Byun & Catherine Zhu & Ryan Sun & Julia Y. Roh & Heather J. Cordell & Hyun-Sung Lee & Vikram R. Shaw & Sung Wook Kang & Javad Razjouyan & Matthew A. Cooley & Manal M. Hassan & , 2023. "Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36678-8
    DOI: 10.1038/s41467-023-36678-8
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    1. Vincent L. Chen & Xiaomeng Du & Yanhua Chen & Annapurna Kuppa & Samuel K. Handelman & Rishel B. Vohnoutka & Patricia A. Peyser & Nicholette D. Palmer & Lawrence F. Bielak & Brian Halligan & Elizabeth , 2021. "Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Fang Qiu & Ruqi Tang & Xianbo Zuo & Xingjuan Shi & Yiran Wei & Xiaodong Zheng & Yaping Dai & Yuhua Gong & Lan Wang & Ping Xu & Xiang Zhu & Jian Wu & Chongxu Han & Yueqiu Gao & Kui Zhang & Yuzhang Jian, 2017. "A genome-wide association study identifies six novel risk loci for primary biliary cholangitis," Nature Communications, Nature, vol. 8(1), pages 1-8, April.
    3. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    4. Carl D. Langefeld & Hannah C. Ainsworth & Deborah S. Cunninghame Graham & Jennifer A. Kelly & Mary E. Comeau & Miranda C. Marion & Timothy D. Howard & Paula S. Ramos & Jennifer A. Croker & David L. Mo, 2017. "Transancestral mapping and genetic load in systemic lupus erythematosus," Nature Communications, Nature, vol. 8(1), pages 1-18, December.
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