Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells
Bhuwan Khatri, Kandice L. Tessneer, Astrid Rasmussen, Farhang Aghakhanian, Tove Ragna Reksten, Adam Adler, Ilias Alevizos, Juan‐Manuel Anaya, Lara A. Aqrawi, Eva Baecklund, Johan G. Brun, Sara Magnusson Bucher, Maija‐Leena Eloranta, Fiona Engelke, Helena Forsblad‐d’Elia, Stuart B. Glenn, Daniel Hammenfors, Juliana Imgenberg‐Kreuz, Janicke Liaaen Jensen, Svein Joar Auglænd Johnsen, Malin V. Jonsson, Marika Kvarnström, Jennifer A. Kelly, He Li, Thomas Mandl, Javier Martı́n, Gaëtane Nocturne, Katrine Brække Norheim, Øyvind Palm, Kathrine Skarstein, A. M. Stolarczyk, Kimberly E. Taylor, María Teruel, Elke Theander, Swamy Venuturupalli, Daniel J. Wallace, Kiely Grundahl, Kimberly S Hefner, Lida Radfar, David M. Lewis, Donald U. Stone, C. Erick Kaufman, Michael T. Brennan, Joel M. Guthridge, Judith A. James, R. Hal Scofield, Patrick M. Gaffney, Lindsey A. Criswell, Roland Jonsson, Per Eriksson, Simon Bowman, Roald Omdal, Lars Rönnblom, Blake M. Warner, Maureen Rischmueller, Torsten Witte, A. Darise Farris, Xavier Mariette, Marta E. Alarcón‐Riquelme, Caroline H. Shiboski, Marie Wahren‐Herlenius, Wan‐Fai Ng, UK Primary Sjögren’s Syndrome Registry, Kathy L. Sivils, Indra Adrianto, Gunnel Nordmark, Christopher J. Lessard
Abstract
Sjögren'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.