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 Jazebi & 40 others Deborah 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

196 Citations (Scopus)

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 1 2013

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Adaptive Immunity
Innate Immunity
Keratoconjunctivitis Sicca
Xerostomia
HLA Antigens
Autoimmune Diseases
Genes

Cite this

Lessard, C. J., Li, H., Adrianto, I., Ice, J. A., Rasmussen, A., Grundahl, K. 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

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome. / Lessard, Christopher J.; Li, He; Adrianto, Indra; Ice, John A.; Rasmussen, Astrid; Grundahl, Kiely M.; Kelly, Jennifer A.; Dozmorov, Mikhail G.; Miceli-Richard, Corinne; Bowman, Simon; Lester, Sue; Eriksson, Per; Eloranta, Maija Leena; Brun, Johan G.; Gøransson, Lasse G.; Harboe, Erna; Guthridge, Joel M.; Kaufman, Kenneth M.; Kvarnström, Marika; Jazebi, Helmi; Graham, Deborah S Cunninghame; Grandits, Martha E.; Nazmul-Hossain, Abu N M; Patel, Ketan; Adler, Adam J.; Maier-Moore, Jacen S.; Farris, A. Darise; Brennan, Michael T.; Lessard, James A.; Chodosh, James; Gopalakrishnan, Rajaram; Hefner, Kimberly S.; Houston, Glen D.; Huang, Andrew J W; Hughes, Pamela J.; Lewis, David M.; Radfar, Lida; Rohrer, Michael D.; Stone, Donald U.; Wren, Jonathan D.; Vyse, Timothy J.; Gaffney, Patrick M.; James, Judith A.; Omdal, Roald; Wahren-Herlenius, Marie; Illei, Gabor G.; Witte, Torsten; Jonsson, Roland; Rischmueller, Maureen; Rönnblom, Lars; Nordmark, Gunnel; Ng, Wan Fai; Mariette, Xavier; Anaya, Juan Manuel; Rhodus, Nelson L.; Segal, Barbara M.; Scofield, R. Hal; Montgomery, Courtney G.; Harley, John B.; Sivils, Kathy L.

In: Nature Genetics, Vol. 45, No. 11, 01.11.2013, p. 1284-1294.

Research output: Contribution to journalArticle

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, Graham, DSC, Grandits, ME, Nazmul-Hossain, ANM, Patel, K, Adler, AJ, Maier-Moore, JS, Farris, AD, Brennan, MT, Lessard, JA, Chodosh, J, Gopalakrishnan, R, Hefner, KS, Houston, GD, Huang, AJW, 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, Mariette, X, Anaya, JM, Rhodus, NL, Segal, BM, Scofield, RH, Montgomery, CG, Harley, JB & Sivils, KL 2013, 'Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome' Nature Genetics, vol. 45, no. 11, pp. 1284-1294. https://doi.org/10.1038/ng.2792
Lessard, Christopher J. ; Li, He ; Adrianto, Indra ; Ice, John A. ; Rasmussen, Astrid ; Grundahl, Kiely M. ; Kelly, Jennifer A. ; Dozmorov, Mikhail G. ; Miceli-Richard, Corinne ; Bowman, Simon ; Lester, Sue ; Eriksson, Per ; Eloranta, Maija Leena ; Brun, Johan G. ; Gøransson, Lasse G. ; Harboe, Erna ; Guthridge, Joel M. ; Kaufman, Kenneth M. ; Kvarnström, Marika ; Jazebi, Helmi ; Graham, Deborah S Cunninghame ; Grandits, Martha E. ; Nazmul-Hossain, Abu N M ; Patel, Ketan ; Adler, Adam J. ; Maier-Moore, Jacen S. ; Farris, A. Darise ; Brennan, Michael T. ; Lessard, James A. ; Chodosh, James ; Gopalakrishnan, Rajaram ; Hefner, Kimberly S. ; Houston, Glen D. ; Huang, Andrew J W ; Hughes, Pamela J. ; Lewis, David M. ; Radfar, Lida ; Rohrer, Michael D. ; Stone, Donald U. ; Wren, Jonathan D. ; Vyse, Timothy J. ; Gaffney, Patrick M. ; James, Judith A. ; Omdal, Roald ; Wahren-Herlenius, Marie ; Illei, Gabor G. ; Witte, Torsten ; Jonsson, Roland ; Rischmueller, Maureen ; Rönnblom, Lars ; Nordmark, Gunnel ; Ng, Wan Fai ; Mariette, Xavier ; Anaya, Juan Manuel ; Rhodus, Nelson L. ; Segal, Barbara M. ; Scofield, R. Hal ; Montgomery, Courtney G. ; Harley, John B. ; Sivils, Kathy L. / Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome. In: Nature Genetics. 2013 ; Vol. 45, No. 11. pp. 1284-1294.
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abstract = "Sj{\"o}gren'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 Sj{\"o}gren'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 Sj{\"o}gren's syndrome.",
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T1 - Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome

AU - Lessard, Christopher J.

AU - Li, He

AU - Adrianto, Indra

AU - Ice, John A.

AU - Rasmussen, Astrid

AU - Grundahl, Kiely M.

AU - Kelly, Jennifer A.

AU - Dozmorov, Mikhail G.

AU - Miceli-Richard, Corinne

AU - Bowman, Simon

AU - Lester, Sue

AU - Eriksson, Per

AU - Eloranta, Maija Leena

AU - Brun, Johan G.

AU - Gøransson, Lasse G.

AU - Harboe, Erna

AU - Guthridge, Joel M.

AU - Kaufman, Kenneth M.

AU - Kvarnström, Marika

AU - Jazebi, Helmi

AU - Graham, Deborah S Cunninghame

AU - Grandits, Martha E.

AU - Nazmul-Hossain, Abu N M

AU - Patel, Ketan

AU - Adler, Adam J.

AU - Maier-Moore, Jacen S.

AU - Farris, A. Darise

AU - Brennan, Michael T.

AU - Lessard, James A.

AU - Chodosh, James

AU - Gopalakrishnan, Rajaram

AU - Hefner, Kimberly S.

AU - Houston, Glen D.

AU - Huang, Andrew J W

AU - Hughes, Pamela J.

AU - Lewis, David M.

AU - Radfar, Lida

AU - Rohrer, Michael D.

AU - Stone, Donald U.

AU - Wren, Jonathan D.

AU - Vyse, Timothy J.

AU - Gaffney, Patrick M.

AU - James, Judith A.

AU - Omdal, Roald

AU - Wahren-Herlenius, Marie

AU - Illei, Gabor G.

AU - Witte, Torsten

AU - Jonsson, Roland

AU - Rischmueller, Maureen

AU - Rönnblom, Lars

AU - Nordmark, Gunnel

AU - Ng, Wan Fai

AU - Mariette, Xavier

AU - Anaya, Juan Manuel

AU - Rhodus, Nelson L.

AU - Segal, Barbara M.

AU - Scofield, R. Hal

AU - Montgomery, Courtney G.

AU - Harley, John B.

AU - Sivils, Kathy L.

PY - 2013/11/1

Y1 - 2013/11/1

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