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

Lessard CJ, Li H, Adrianto I, Ice JA, Rasmussen A, Grundahl KM, Kelly JA, Dozmorov MG, Miceli-Richard C, Bowman S, Lester S, Eriksson P, Eloranta ML, Brun JG, Gøransson LG, Harboe E, Guthridge JM, Kaufman KM, Kvarnström M, Jazebi H, Cunninghame Graham DS, Grandits ME, Nazmul-Hossain AN, Patel K, Adler AJ, Maier-Moore JS, Farris AD, Brennan MT, Lessard JA, Chodosh J, Gopalakrishnan R, Hefner KS, Houston GD, Huang AJ, Hughes PJ, Lewis DM, Radfar L, Rohrer MD, Stone DU, Wren JD, Vyse TJ, Gaffney PM, James JA, Omdal R, Wahren-Herlenius M, Illei GG, Witte T, Jonsson R, Rischmueller M, Rönnblom L, Nordmark G, Ng WF, UK Primary Sjögren's Syndrome Registry , Mariette X, Anaya JM, Rhodus NL, Segal BM, Scofield RH, Montgomery CG, Harley JB, Sivils KL

Nat. Genet. 45 (11) 1284-1292 [2013-11-00; online 2013-10-08]

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.

NGI Uppsala (SNP&SEQ Technology Platform)

National Genomics Infrastructure

PubMed 24097067

DOI 10.1038/ng.2792

Crossref 10.1038/ng.2792

pii: ng.2792
pmc: PMC3867192
mid: EMS54762