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

Christopher J. Lessard, He Li, Indra Adrianto, John A. Ice, Astrid Rasmussen, Kiely M. 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 JazebiDeborah S.Cunninghame Graham, Martha E. Grandits, Abu N.M. Nazmul-Hossain, Ketan Patel, Adam J. Adler, Jacen S. Maier-Moore, A. Darise Farris, Michael T. Brennan, James A. Lessard, James Chodosh, Rajaram Gopalakrishnan, Kimberly S. Hefner, Glen D. Houston, Andrew J.W. Huang, Pamela J. 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

Research output: Contribution to journalArticle

236 Scopus citations

Abstract

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 (P meta = 7.65 × 10 -114), we establish associations with IRF5-TNPO3 (P meta = 2.73 × 10 -19), STAT4 (P meta = 6.80 × 10 -15), IL12A (P meta = 1.17 × 10 -10), FAM167A-BLK (P meta = 4.97 × 10 -10), DDX6-CXCR5 (P meta = 1.10 × 10 -8) and TNIP1 (P meta = 3.30 × 10 -8). We also observed suggestive associations (P meta < 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.

Original languageEnglish (US)
Pages (from-to)1284-1294
Number of pages11
JournalNature genetics
Volume45
Issue number11
DOIs
StatePublished - Nov 2013

ASJC Scopus subject areas

  • Genetics

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    Lessard, C. J., Li, H., Adrianto, I., Ice, J. A., Rasmussen, A., Grundahl, K. M., Kelly, J. A., Dozmorov, M. G., Miceli-Richard, C., Bowman, S., Lester, S., Eriksson, P., Eloranta, M. L., Brun, J. G., Gøransson, L. G., Harboe, E., Guthridge, J. M., Kaufman, K. M., Kvarnström, M., ... Sivils, K. L. (2013). Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome. Nature genetics, 45(11), 1284-1294. https://doi.org/10.1038/ng.2792