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

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.