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

Khatri, Bhuwan; Tessneer, Kandice L.; Rasmussen, Astrid; Aghakhanian, Farhang; Reksten, Tove Ragna; Adler, Adam; Alevizos, Ilias; Anaya, Juan-Manuel; Aqrawi, Lara A.; Baecklund, Eva; Brun, Johan Gorgas; Bucher, Sara Magnusson; Eloranta, Maija-Leena; Engelke, Fiona; Forsblad-d’Elia, Helena; Glenn, Stuart B.; Hammenfors, Daniel; Imgenberg-Kreuz, Juliana; Jensen, Janicke Liaaen; Johnsen, Svein Joar Auglæn; Jonsson, Malin Viktoria; Kvarnström, Marika; Kelly, Jennifer A.; Li, He; Mandl, Thomas; Martín, Javier; Nocturne, Gaétane; Norheim, Katrine Brække; Palm, Øyvind; Skarstein, Kathrine; Stolarczyk, Anna M.; Taylor, Kimberly E.; Teruel, Maria; Theander, Elke; Venuturupalli, Swamy; Wallace, Daniel J.; Grundahl, Kiely M.; Hefner, Kimberly S.; Radfar, Lida; Lewis, David M.; Stone, Donald U.; Kaufman, C. Erick; Brennan, Michael T.; Guthridge, Joel M.; James, Judith A.; Scofield, R. Hal; Gaffney, Patrick M.; Criswell, Lindsey A.; Jonsson, Roland; Eriksson, Per; Bowman, Simon J.; Omdal, Roald; Rönnblom, Lars; Warner, Blake; Rischmueller, Maureen; Witte, Torsten; Farris, A. Darise; Mariette, Xavier; Alarcon-Riquelme, Marta E.; Shiboski, Caroline H.; Herlenius, Marie Elisabeth Wahren; Ng, Wan-Fai; Sivils, Kathy L.; Adrianto, Indra; Nordmark, Gunnel; Lessard, Christopher J.
Journal article, Peer reviewed
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https://hdl.handle.net/11250/3022175
Date
2022
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Nature Communications. 2022, 13, 4287.   10.1038/s41467-022-30773-y
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.
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Nature
Journal
Nature Communications
Copyright
Copyright 2022 The Author(s)
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