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

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References

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Acknowledgements

We are grateful to all the individuals with Sjögren's syndrome and those serving as healthy controls who participated in this study. We thank the following individuals for their help in the collection and ascertainment of the samples used in this study: E. Rothrock, J. Harris, S. Johnson, S. Cioli, N. Weber, D. Williams, W. Daniels, C. Pritchett-Frazee, K. Crouch, L. Battiest, J. Rodgers, J. Robertson, T. Nguyen, A. Crosbie, E. James, C. Meyer, A. McElroy, E. Emamian, J. Ermer, K. Rohlf, J. Leon, A. Petersen, D. Hartle, J. Novizke, W. Ortman, C. Espy, B. Cobb, G. Kristjansdottir, M. Eidsheim, J. Benessiano, Centre de Ressources Biologiques, Hôpital Bichat, Paris, and the SNP&SEQ Technology Platform, Uppsala, Sweden. We also thank S. Glenn and J. Ning for their ongoing assistance in developing and maintaining the computational infrastructure used to perform this study.

We thank the following funding agencies for their support: this publication was made possible by grants P50 AR0608040 (K.L.S., C.J.L., R.H.S. and A.D.F.), 5R01 DE015223 (K.L.S. and J.B.H.), 5RC2 AR058959 (P.M.G.), 5P01 AR049084-10 (J.B.H.), 5P30 AR053483 (J.A.J. and J.M.G.), 5U19 AI082714 (K.L.S., J.A.J. and C.J.L.), 1R01 DE018209-02 (K.L.S. and J.B.H.), 5R01 DE018209 (K.L.S.), 8P20 GM103456 (P.M.G., C.J.L., J.D.W. and I.A.), P20 GM103636 (M.G.D. and J.D.W.), 5R37 AI024717-25 (J.B.H.), 5P01 AI083194-03 (K.L.S. and J.B.H.), 7S10 RR027190-02 (J.B.H.), 1U01 AI101934 (J.A.J. and J.M.G.), 1RC1 AR058554 (J.A.J. and J.M.G.) and 5P30 GM103510 (J.A.J. and J.M.G.) from the NIH. The contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH. Additional funding was obtained from Intramural Research Program of the National Institute of Dental and Craniofacial Research (G.G.I.), US Department of Veterans Affairs IMMA 9 (J.B.H.), US Department of Defense PR094002 (J.B.H.), American College of Rheumatology Research and Education Foundation/Abbott Health Professional Graduate Student Preceptorship Award 2009 (C.J.L. and K.L.S.), Oklahoma Medical Research Foundation (C.J.L. and K.L.S.), Sjögren's Syndrome Foundation (K.L.S.), Phileona Foundation (K.L.S.), the French ministry of health (PHRC 2006-AOM06133) and the French ministry of research (ANR-2010-BLAN-1133) (X.M. and C.M.-R.), The Strategic Research Program at Helse Bergen, Western Norway Regional Health Authority (L.G.G., J.G.B. and R.J.), The Broegelmann Foundation (J.G.B. and R.J.), Norwegian Foundation for Health and Rehabilitation (E.H.), KFO 250 TP03, WI 1031/6-1 (T.W.), KFO 250, Z1 (T.W.), Medical Research Council, UK G0800629 (W.-F.N. and S.B.), Northumberland, Tyne and Wear Comprehensive Local Research Network (CLRN) (W.-F.N.), The Swedish Research Council (M.W.-H. and L. Rönnblom), The King Gustaf the V-th 80-year Foundation (M.W.-H.), Knut and Alice Wallenberg Foundation (L. Rönnblom) and The Swedish Rheumatism Association (M.W.-H., G.N., L. Rönnblom and P.E.). This study made use of genotypes available through dbGAP, with acknowledgments provided in the Supplementary Note.

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Authors and Affiliations

1. Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
   Christopher J Lessard, He Li, Indra Adrianto, John A Ice, Astrid Rasmussen, Kiely M Grundahl, Jennifer A Kelly, Mikhail G Dozmorov, Joel M Guthridge, Adam J Adler, Jacen S Maier-Moore, A Darise Farris, Jonathan D Wren, Patrick M Gaffney, Judith A James, R Hal Scofield, Courtney G Montgomery & Kathy L Sivils
2. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
   Christopher J Lessard, He Li, Judith A James & Kathy L Sivils
3. Université Paris-Sud, Assistance Publique–Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris-Sud, Institut National de la Santé et de la Recherche Médicale (INSERM) U1012, Paris, France
   Corinne Miceli-Richard & Xavier Mariette
4. Rheumatology Department, University Hospital Birmingham, Birmingham, UK
   Simon Bowman
5. Department of Rheumatology, The Queen Elizabeth Hospital, South Australia
   Sue Lester & Maureen Rischmueller
6. Department of Rheumatology, Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
   Per Eriksson
7. Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
   Maija-Leena Eloranta, Lars Rönnblom & Gunnel Nordmark
8. Department of Clinical Science, Section for Rheumatology, University of Bergen, Bergen, Norway
   Johan G Brun
9. Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
   Johan G Brun & Roland Jonsson
10. Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, Stavanger, Norway
    Lasse G Gøransson, Erna Harboe & Roald Omdal
11. Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
    Kenneth M Kaufman & John B Harley
12. Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA
    Kenneth M Kaufman & John B Harley
13. Department of Medicine, Karolinska Institutet, Stockholm, Sweden
    Marika Kvarnström, Helmi Jazebi & Marie Wahren-Herlenius
14. Department of Rheumatology, Örebro University Hospital, Örebro, Sweden
    Helmi Jazebi
15. Department of Medical and Molecular Genetics, King's College London, London, UK
    Deborah S Cunninghame Graham & Timothy J Vyse
16. United Medical Specialties, St. Paul, Minnesota, USA
    Martha E Grandits
17. School of Dental Medicine, University of Colorado–Denver, Denver, Colorado, USA
    Abu N M Nazmul-Hossain
18. Department of Developmental and Surgical Science, Division of Oral and Maxillofacial Surgery, University of Minnesota School of Dentistry, Minneapolis, Minnesota, USA
    Ketan Patel & Pamela J Hughes
19. Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
    Jacen S Maier-Moore, Judith A James & R Hal Scofield
20. Department of Oral Medicine, Carolinas Medical Center, Charlotte, North Carolina, USA
    Michael T Brennan
21. Valley Bone and Joint Clinic, Grand Forks, North Dakota, USA
    James A Lessard
22. Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
    James Chodosh
23. Department of Diagnostic and Biological Sciences, Division of Oral and Maxillofacial Pathology, University of Minnesota School of Dentistry, Minneapolis, Minnesota, USA
    Rajaram Gopalakrishnan
24. Hefner Eye Care and Optical Center, Oklahoma City, Oklahoma, USA
    Kimberly S Hefner
25. Department of Oral and Maxillofacial Pathology, University of Oklahoma College of Dentistry, Oklahoma City, Oklahoma, USA
    Glen D Houston & David M Lewis
26. Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, Missouri, USA
    Andrew J W Huang
27. Oral Diagnosis and Radiology Department, University of Oklahoma College of Dentistry, Oklahoma City, Oklahoma, USA
    Lida Radfar
28. Hard Tissue Research Laboratory, University of Minnesota School of Dentistry, Minneapolis, Minnesota, USA
    Michael D Rohrer
29. Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
    Donald U Stone
30. Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
    Jonathan D Wren
31. National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH), Bethesda, Maryland, USA
    Gabor G Illei
32. Department of Clinical Immunology and Rheumatology, Hannover Medical School, Hannover, Germany
    Torsten Witte
33. Department of Clinical Science, Broegelmann Research Laboratory, University of Bergen, Bergen, Norway
    Roland Jonsson
34. Department of Rheumatology, The Queen Elizabeth Hospital and Discipline of Medicine, University of Adelaide, South Australia
    Maureen Rischmueller
35. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
    Wan-Fai Ng
36. Center for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, Colombia
    Juan-Manuel Anaya
37. Department of Oral Surgery, University of Minnesota School of Dentistry, Minneapolis, Minnesota, USA
    Nelson L Rhodus
38. Division of Rheumatology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
    Barbara M Segal
39. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA
    R Hal Scofield

Authors

1. Christopher J Lessard
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2. He Li
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3. Indra Adrianto
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4. John A Ice
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5. Astrid Rasmussen
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6. Kiely M Grundahl
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7. Jennifer A Kelly
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8. Mikhail G Dozmorov
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9. Corinne Miceli-Richard
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10. Simon Bowman
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11. Sue Lester
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12. Per Eriksson
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13. Maija-Leena Eloranta
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14. Johan G Brun
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15. Lasse G Gøransson
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16. Erna Harboe
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17. Joel M Guthridge
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18. Kenneth M Kaufman
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19. Marika Kvarnström
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20. Helmi Jazebi
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21. Deborah S Cunninghame Graham
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22. Martha E Grandits
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23. Abu N M Nazmul-Hossain
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24. Ketan Patel
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25. Adam J Adler
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26. Jacen S Maier-Moore
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27. A Darise Farris
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Consortia

for UK Primary Sjögren's Syndrome Registry

Contributions

C.J.L., K.M.G., J.A.K., C.G.M., J.B.H. and K.L.S. were responsible for the study design. C.J.L., J.A.I., A.R., K.M.G., C.M.-R., S.B., S.L., J.G.B., L.G.G., E.H., J.M.G., D.S.C.G., M.E.G., A.N.M.N.-H., K.P., J.S.M.-M., A.D.F., M.-L.E., J.A.L., J.C., R.G., K.S.H., G.D.H., M.T.B., A.J.W.H., P.J.H., D.M.L., L. Radfar, M.D.R., D.U.S., T.J.V., P.M.G., J.A.J., R.O., M.W.-H., M.K., H.J., G.G.I., T.W., R.J., M.R., G.N., P.E., W.-F.N., X.M., J.-M.A., L. Rönnblom, N.L.R., B.M.S., R.H.S., J.B.H. and K.L.S. assisted in the collection and characterization of the Sjögren's syndrome cases and healthy controls. K.M.K., A.J.A. and P.M.G. performed the genotyping. C.J.L., H.L., I.A. and J.A.I. performed all analyses and imputation under the guidance of C.G.M. and K.L.S. M.G.D. and J.D.W. performed the enrichment analysis. C.J.L., H.L., I.A., J.A.I., J.A.K., C.G.M. and K.L.S. prepared the manuscript, and all authors approved the final draft.

Corresponding author

Correspondence toKathy L Sivils.

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The authors declare no competing financial interests.

Additional information

Further details appear in the Supplementary Note.

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Lessard, C., Li, H., Adrianto, I. et al. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome.Nat Genet 45, 1284–1292 (2013). https://doi.org/10.1038/ng.2792

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• Received: 27 April 2013
• Accepted: 11 September 2013
• Published: 06 October 2013
• Issue Date: November 2013
• DOI: https://doi.org/10.1038/ng.2792