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

Khatri, BhuwanTessneer, Kandice LRasmussen, AstridAghakhanian, FarhangReksten, Tove RagnaAdler, AdamAlevizos, IliasAnaya, Juan-ManuelAqrawi, Lara ABaecklund, EvaBrun, Johan GBucher, Sara MagnussonEloranta, Maija-LeenaEngelke, FionaForsblad-d'Elia, HelenaGlenn, Stuart BHammenfors, DanielImgenberg-Kreuz, JulianaJensen, Janicke LiaaenJohnsen, Svein Joar AuglændJonsson, Malin VKvarnström, MarikaKelly, Jennifer ALi, HeMandl, ThomasMartín, JavierNocturne, GaétaneNorheim, Katrine BrækkePalm, ØyvindSkarstein, KathrineStolarczyk, Anna MTaylor, Kimberly ETeruel, MariaTheander, ElkeVenuturupalli, SwamyWallace, Daniel JGrundahl, Kiely MHefner, Kimberly SRadfar, LidaLewis, David MStone, Donald UKaufman, C ErickBrennan, Michael TGuthridge, Joel MJames, Judith AScofield, R HalGaffney, Patrick MCriswell, Lindsey AJonsson, RolandEriksson, PerBowman, Simon JOmdal, RoaldRönnblom, LarsWarner, BlakeRischmueller, MaureenWitte, TorstenFarris, A DariseMariette, XavierAlarcon-Riquelme, Marta EPRECISESADS Clinical ConsortiumShiboski, Caroline HSjögren’s International Collaborative Clinical Alliance (SICCA)Wahren-Herlenius, MarieNg, Wan-FaiUK Primary Sjögren’s Syndrome RegistrySivils, Kathy LAdrianto, IndraNordmark, GunnelLessard, Christopher J2023-05-032023-05-032022-07-27http://hdl.handle.net/10668/19538Sjögren'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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Genetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideSjogren's SyndromeGenome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.research article35896530open access10.1038/s41467-022-30773-y2041-1723PMC9329286https://www.nature.com/articles/s41467-022-30773-y.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329286/pdf