Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells
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Published:2022-07-27
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Khatri BhuwanORCID, Tessneer Kandice L., Rasmussen Astrid, Aghakhanian Farhang, Reksten Tove RagnaORCID, Adler Adam, Alevizos Ilias, Anaya Juan-ManuelORCID, Aqrawi Lara A., Baecklund Eva, Brun Johan G., Bucher Sara Magnusson, Eloranta Maija-Leena, Engelke FionaORCID, Forsblad-d’Elia Helena, Glenn Stuart B., Hammenfors Daniel, Imgenberg-Kreuz Juliana, Jensen Janicke LiaaenORCID, Johnsen Svein Joar AuglændORCID, Jonsson Malin V.ORCID, Kvarnström MarikaORCID, Kelly Jennifer A., Li He, Mandl ThomasORCID, Martín Javier, Nocturne GaétaneORCID, Norheim Katrine Brække, Palm Øyvind, Skarstein Kathrine, Stolarczyk Anna M., Taylor Kimberly E., Teruel MariaORCID, Theander Elke, Venuturupalli Swamy, Wallace Daniel J., Grundahl Kiely M., Hefner Kimberly S., Radfar Lida, Lewis David M., Stone Donald U., Kaufman C. Erick, Brennan Michael T., Guthridge Joel M., James Judith A.ORCID, Scofield R. Hal, Gaffney Patrick M., Criswell Lindsey A.ORCID, Jonsson Roland, Eriksson Per, Bowman Simon J., Omdal Roald, Rönnblom LarsORCID, Warner BlakeORCID, Rischmueller Maureen, Witte Torsten, Farris A. Darise, Mariette XavierORCID, Alarcon-Riquelme Marta E.ORCID, Shiboski Caroline H., Wahren-Herlenius MarieORCID, Ng Wan-Fai, Sivils Kathy L., Adrianto IndraORCID, Nordmark GunnelORCID, Lessard Christopher J.ORCID, , ,
Abstract
AbstractSjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.
Funder
Norges Forskningsråd Cancerfonden U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases U.S. Department of Health & Human Services | National Institutes of Health Reumatikerförbundet Svenska Läkaresällskapet
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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