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Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome

2013; Nature Portfolio; Volume: 45; Issue: 11 Linguagem: Inglês

10.1038/ng.2792

1546-1718

Christopher J. Lessard, He Li, Indra Adrianto, John A. Ice, Astrid Rasmussen, Kiely Grundahl, Jennifer A. Kelly, Mikhail G. Dozmorov, Corinne Miceli‐Richard, Simon Bowman, Sue Lester, Per Eriksson, Maija‐Leena Eloranta, Johan G. Brun, Lasse G. Gøransson, Erna Harboe, Joel M. Guthridge, Kenneth M. Kaufman, Marika Kvarnström, Helmi Jazebi, Deborah S. Cunninghame Graham, Martha Grandits, Abu N M Nazmul-Hossain, Ketan Patel, Adam J. Adler, Jacen S. Maier‐Moore, A. Darise Farris, Michael T. Brennan, James Lessard, James Chodosh, Rajaram Gopalakrishnan, Kimberly S Hefner, J. Graeme Houston, Andrew Huang, Pamela Hughes, David M. Lewis, Lida Radfar, Michael D. Rohrer, Donald U. Stone, Jonathan D. Wren, Timothy J. Vyse, Patrick M. Gaffney, Judith A. James, Roald Omdal, Marie Wahren‐Herlenius, Gabor G Illei, Torsten Witte, Roland Jonsson, Maureen Rischmueller, Lars Rönnblom, Gunnel Nordmark, Wan‐Fai Ng, Xavier Mariette, Juan‐Manuel Anaya, Nelson L. Rhodus, Barbara M Segal, R. Hal Scofield, Courtney G. Montgomery, John B. Harley, Kathy L Sivils,

Immune Response and Inflammation

Sjögren's syndrome is a common autoimmune disease (affecting ∼0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjögren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10(-114)), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 × 10(-19)), STAT4 (Pmeta = 6.80 × 10(-15)), IL12A (Pmeta = 1.17 × 10(-10)), FAM167A-BLK (Pmeta = 4.97 × 10(-10)), DDX6-CXCR5 (Pmeta = 1.10 × 10(-8)) and TNIP1 (Pmeta = 3.30 × 10(-8)). We also observed suggestive associations (Pmeta < 5 × 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjögren's syndrome.