Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome.
Christopher J Lessard
(1)
,
He Li
,
Indra Adrianto
,
John A Ice
,
Astrid Rasmussen
,
Kiely M Grundahl
,
Jennifer A Kelly
(2)
,
Mikhail G Dozmorov
,
Corinne Miceli-Richard
(3)
,
Simon Bowman
(4)
,
Sue Lester
(5)
,
Per Eriksson
,
Maija-Leena Eloranta
(6)
,
Johan G Brun
(7)
,
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
(8)
,
James James
(9)
,
Judith A James
(9)
,
Rajaram Gopalakrishnan
(10)
,
Kimberly S Hefner
,
Glen D Houston
,
Andrew J W Huang
(11)
,
Pamela J Hughes
(12)
,
David M Lewis
(13)
,
Lida Radfar
,
Michael D Rohrer
,
Donald U Stone
(14)
,
Jonathan D Wren
,
Timothy J Vyse
(15)
,
Patrick M Gaffney
(16, 17)
,
Roald Omdal
,
Marie Wahren-Herlenius
,
Gabor G Illei
,
Torsten Witte
,
Roland Jonsson
(18)
,
Maureen Rischmueller
,
Lars Rönnblom
(6)
,
Gunnel Nordmark
(6)
,
Wan-Fai Ng
,
Xavier Mariette
(3)
,
Juan-Manuel Anaya
,
Nelson L Rhodus
,
Barbara M Segal
,
R Hal Scofield
,
Courtney G Montgomery
(19)
,
John B Harley
(20)
,
Kathy L Sivils
,
He Lessard
,
Deborah S Cunninghame Graham
,
Alain Saraux
(21, 22, 23)
1
OUHSC -
University of Oklahoma Health Sciences Center
2 Macquarie University
3 Service de rhumatologie
4 NQEH - BIRMINGHAM - New Queen Elizabeth Hospital
5 Marine Science Institute
6 Department of Medical Sciences
7 UNIGE - Université de Genève = University of Geneva
8 Institute of Sound and Vibration Research
9 CCI - Centre for Cybersecurity and Cybercrime Investigation [Dublin]
10 Computing and Mathematical Sciences [Pasadena]]
11 Zhejiang University [Hangzhou, China]
12 University of Southampton
13 IMS - Laboratoire de l'intégration, du matériau au système
14 CSAG - Climate Systems Analysis Group [Cape Town]
15 Faculty of Medicine
16 Department of Pathology
17 Department of Pathology, Immunology and Microbiology
18 FOI - Swedish Defence Research Agency [Stockholm]
19 Department of Public Health & Policy
20 University of Alberta
21 CIC - Brest - Centre d'Investigation Clinique
22 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
23 CHU - BREST - Rhumato - CHRU Brest - Service de Rhumatologie
2 Macquarie University
3 Service de rhumatologie
4 NQEH - BIRMINGHAM - New Queen Elizabeth Hospital
5 Marine Science Institute
6 Department of Medical Sciences
7 UNIGE - Université de Genève = University of Geneva
8 Institute of Sound and Vibration Research
9 CCI - Centre for Cybersecurity and Cybercrime Investigation [Dublin]
10 Computing and Mathematical Sciences [Pasadena]]
11 Zhejiang University [Hangzhou, China]
12 University of Southampton
13 IMS - Laboratoire de l'intégration, du matériau au système
14 CSAG - Climate Systems Analysis Group [Cape Town]
15 Faculty of Medicine
16 Department of Pathology
17 Department of Pathology, Immunology and Microbiology
18 FOI - Swedish Defence Research Agency [Stockholm]
19 Department of Public Health & Policy
20 University of Alberta
21 CIC - Brest - Centre d'Investigation Clinique
22 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
23 CHU - BREST - Rhumato - CHRU Brest - Service de Rhumatologie
He Li
- Function : Author
Indra Adrianto
- Function : Author
John A Ice
- Function : Author
Astrid Rasmussen
- Function : Author
Kiely M Grundahl
- Function : Author
Mikhail G Dozmorov
- Function : Author
Per Eriksson
- Function : Author
Lasse G Gøransson
- Function : Author
Erna Harboe
- Function : Author
Joel M Guthridge
- Function : Author
Kenneth M Kaufman
- Function : Author
Marika Kvarnström
- Function : Author
Helmi Jazebi
- Function : Author
Deborah S Cunninghame Graham
- Function : Author
Martha E Grandits
- Function : Author
Abu N M Nazmul-Hossain
- Function : Author
Ketan Patel
- Function : Author
Adam J Adler
- Function : Author
Jacen S Maier-Moore
- Function : Author
a Darise Farris
- Function : Author
Kimberly S Hefner
- Function : Author
Glen D Houston
- Function : Author
Lida Radfar
- Function : Author
Michael D Rohrer
- Function : Author
Jonathan D Wren
- Function : Author
Roald Omdal
- Function : Author
Marie Wahren-Herlenius
- Function : Author
Gabor G Illei
- Function : Author
Torsten Witte
- Function : Author
Maureen Rischmueller
- Function : Author
Wan-Fai Ng
- Function : Author
Xavier Mariette
- Function : Author
- PersonId : 756829
- ORCID : 0000-0002-4244-5417
- IdRef : 113094116
Juan-Manuel Anaya
- Function : Author
- PersonId : 767596
- ORCID : 0000-0002-6444-1249
- IdRef : 234685212
Nelson L Rhodus
- Function : Author
Barbara M Segal
- Function : Author
R Hal Scofield
- Function : Author
Kathy L Sivils
- Function : Author
He Lessard
- Function : Author
Deborah S Cunninghame Graham
- Function : Author
Alain Saraux
- Function : Other
- PersonId : 929631
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 (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.