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; 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

doi:10.1038/ng.2792

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

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

Oklahoma Medical Research Foundation
University of Oklahoma
Université Paris-Saclay
University Hospitals Birmingham NHS Foundation Trust
Queen Elizabeth Hospital Australia
Linköping University
Uppsala University
University of Bergen
Stavanger University Hospital
Cincinnati Children's Hospital Medical Center
VA Medical Center
Karolinska Institutet
Örebro University
King's College London
St. Paul, MN
University of Colorado Denver
University of Minnesota Twin Cities
Carolinas Medical Center
Valley Bone and Joint Clinic
Harvard University
Hefner Eye Care and Optical Center
Washington University St. Louis
National Institutes of Health
Hannover Medical School
University of Adelaide
Newcastle University
Universidad del Rosario
Department of Veterans Affairs

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	1284-1294
Number of pages	11
Journal	Nature Genetics
Volume	45
Issue number	11
DOIs	https://doi.org/10.1038/ng.2792
Publication status	Published - Nov 2013
Externally published	Yes

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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

@article{9fa2391bdff943b0845458b7b34342c2,

title = "Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sj{\"o}gren's syndrome",

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.",

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

year = "2013",

month = nov,

doi = "10.1038/ng.2792",

language = "English",

volume = "45",

pages = "1284--1294",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "11",

}

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

TY - JOUR

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

Y1 - 2013/11

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84887116043

U2 - 10.1038/ng.2792

DO - 10.1038/ng.2792

M3 - Article

C2 - 24097067

AN - SCOPUS:84887116043

SN - 1061-4036

VL - 45

SP - 1284

EP - 1294

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

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

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