학술논문
Genome-wide association study identifies Sjögrens risk loci with functional implications in immune and glandular cells.
Document Type
article
Author
Khatri, Bhuwan; Tessneer, Kandice; Rasmussen, Astrid; Aghakhanian, Farhang; Reksten, Tove; Adler, Adam; Alevizos, Ilias; Anaya, Juan-Manuel; Aqrawi, Lara; Baecklund, Eva; Brun, Johan; Bucher, Sara; Eloranta, Maija-Leena; Engelke, Fiona; Forsblad-dElia, Helena; Glenn, Stuart; Hammenfors, Daniel; Imgenberg-Kreuz, Juliana; Jensen, Janicke; Johnsen, Svein; Jonsson, Malin; Kvarnström, Marika; Kelly, Jennifer; Li, He; Mandl, Thomas; Martín, Javier; Nocturne, Gaétane; Norheim, Katrine; Palm, Øyvind; Skarstein, Kathrine; Stolarczyk, Anna; Taylor, Kimberly; Teruel, Maria; Theander, Elke; Venuturupalli, Swamy; Wallace, Daniel; Grundahl, Kiely; Hefner, Kimberly; Radfar, Lida; Lewis, David; Stone, Donald; Kaufman, C; Brennan, Michael; Guthridge, Joel; James, Judith; Scofield, R; Gaffney, Patrick; Criswell, Lindsey; Jonsson, Roland; Eriksson, Per; Bowman, Simon; Omdal, Roald; Rönnblom, Lars; Warner, Blake; Rischmueller, Maureen; Witte, Torsten; Farris, A; Mariette, Xavier; Alarcon-Riquelme, Marta; Shiboski, Caroline; Wahren-Herlenius, Marie; Ng, Wan-Fai; Sivils, Kathy; Adrianto, Indra; Nordmark, Gunnel; Lessard, Christopher
Source
Nature Communications. 13(1)
Subject
Language
Abstract
Sjögrens 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 Sjögrens 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.