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Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis.
Han, Younghun; Byun, Jinyoung; Zhu, Catherine; Sun, Ryan; Roh, Julia Y; Cordell, Heather J; Lee, Hyun-Sung; Shaw, Vikram R; Kang, Sung Wook; Razjouyan, Javad; Cooley, Matthew A; Hassan, Manal M; Siminovitch, Katherine A; Folseraas, Trine; Ellinghaus, David; Bergquist, Annika; Rushbrook, Simon M; Franke, Andre; Karlsen, Tom H; Lazaridis, Konstantinos N; McGlynn, Katherine A; Roberts, Lewis R; Amos, Christopher I.
Afiliación
  • Han Y; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
  • Byun J; Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
  • Zhu C; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
  • Sun R; Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
  • Roh JY; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
  • Cordell HJ; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
  • Lee HS; Department of Biostatistics, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
  • Shaw VR; Department of Pharmacy, Ochsner Health, New Orleans, LA, USA.
  • Kang SW; Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Razjouyan J; David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
  • Cooley MA; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
  • Hassan MM; David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
  • Siminovitch KA; VA HSR&D, Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, TX, USA.
  • Folseraas T; Big Data Scientist Training Enhancement Program (BD-STEP), VA Office of Research and Development, Washington, DC, USA.
  • Ellinghaus D; Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
  • Bergquist A; VA Quality Scholars Coordinating Center, IQuESt, Michael E. DeBakey VA Medical Center, Houston, TX, USA.
  • Rushbrook SM; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA.
  • Franke A; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Karlsen TH; Departments of Medicine, Immunology and Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
  • Lazaridis KN; Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute and Toronto General Research Institute, Toronto, Ontario, Canada.
  • McGlynn KA; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
  • Roberts LR; Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Amos CI; Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich, United Kingdom.
Nat Commun ; 14(1): 1069, 2023 02 24.
Article en En | MEDLINE | ID: mdl-36828809
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Colangitis Esclerosante / Estudio de Asociación del Genoma Completo Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Colangitis Esclerosante / Estudio de Asociación del Genoma Completo Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido