Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

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. The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.Funding Agencies|National Institutes of Health (NIH) [HHSN268200782096C, HHSN268201100011I, HHSN268201200008I, R01AR073855, R01AR065953, R01AR074310, P50AR060804, R01AR050782, R01DE018209, R33AR076803, R21AR079089]; NIDCR Sjogrens Syndrome Clinic; NIDCR Division of Intramural Research at the National Institutes of Health funds [Z01-DE000704]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanys Excellence Strategy [EXC 2155, 390874280]; Research Council of Norway (Oslo, Norway) [240421, 316120]; Western Norway Regional Health Authority (Helse Vest) [911807, 912043]; Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; King Gustav Vs 80-year Foundation; Swedish Society of Medicine; Swedish Cancer Society; Sjogrens Syndrome Foundation; Phileona Foundation; Stockholm County Council; Swedish Research Council [2017-000641]; Assistance Publique-Hopitaux de Paris (Ministry of Health) [P060228]; French society of Rheumatology; National Institute of Aging [RC2 AG036495, RC4 AG039029]; National Institute of Dental and Craniofacial Research (NIDCR); National Eye Institute; Office of Research on Womens Health [N01-DE-32636]; NIDCR through CIDRs NIH contract; FOREUM Foundation for Research in Rheumatology