Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus (original) (raw)

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In the version of this article initially published online, the name of author Annemie J. Schuerwegh was misspelled. The error has been corrected for the print, PDF, and HTML versions of this article.

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References

  1. Gabrielli, A., Avvedimento, E.V. & Krieg, T. Scleroderma. N. Engl. J. Med. 360, 1989–2003 (2009).
    Article CAS Google Scholar
  2. Jimenez, S.A. & Derk, C.T. Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis. Ann. Intern. Med. 140, 37–50 (2004).
    Article CAS Google Scholar
  3. Agarwal, S.K., Tan, F.K. & Arnett, F.C. Genetics and genomic studies in scleroderma (systemic sclerosis). Rheum. Dis. Clin. North Am. 34, 17–40 (2008).
    Article Google Scholar
  4. Arnett, F.C. et al. Major Histocompatibility Complex (MHC) class II alleles, haplotypes, and epitopes which confer susceptibility or protection in the fibrosing autoimmune disease systemic sclerosis: analyses in 1300 Caucasian, African-American and Hispanic cases and 1000 controls. Ann. Rheum. Dis. published online (12 July 2009).
  5. Rueda, B. et al. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype. Hum. Mol. Genet. 18, 2071–2077 (2009).
    Article CAS Google Scholar
  6. Tsuchiya, N. et al. Association of STAT4 polymorphism with systemic sclerosis in a Japanese population. Ann. Rheum. Dis. 68, 1375–1376 (2009).
    Article CAS Google Scholar
  7. Ito, I. et al. Association of a functional polymorphism in the IRF5 region with systemic sclerosis in a Japanese population. Arthritis Rheum. 60, 1845–1850 (2009).
    Article CAS Google Scholar
  8. Dieudé, P. et al. Association between the IRF5 rs2004640 functional polymorphism and systemic sclerosis: a new perspective for pulmonary fibrosis. Arthritis Rheum. 60, 225–233 (2009).
    Article Google Scholar
  9. Gregersen, P.K. & Olsson, L.M. Recent advances in the genetics of autoimmune disease. Annu. Rev. Immunol. 27, 363–391 (2009).
    Article CAS Google Scholar
  10. Hunter, D.J. et al. A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat. Genet. 39, 870–874 (2007).
    Article CAS Google Scholar
  11. Yeager, M. et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat. Genet. 39, 645–649 (2007).
    Article CAS Google Scholar
  12. Stefansson, H. et al. Large recurrent microdeletions associated with schizophrenia. Nature 455, 232–236 (2008).
    Article CAS Google Scholar
  13. Krawczak, M. et al. PopGen: population-based recruitment of patients and controls for the analysis of complex genotype-phenotype relationships. Community Genet. 9, 55–61 (2006).
    PubMed Google Scholar
  14. Wellcome Trust Case-Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).
  15. Call, M.E. & Wucherpfennig, K.W. Molecular mechanisms for the assembly of the T cell receptor-CD3 complex. Mol. Immunol. 40, 1295–1305 (2004).
    Article CAS Google Scholar
  16. Krishnan, S. et al. Increased caspase-3 expression and activity contribute to reduced CD3zeta expression in systemic lupus erythematosus T cells. J. Immunol. 175, 3417–3423 (2005).
    Article CAS Google Scholar
  17. Krishnan, S. et al. Generation and biochemical analysis of human effector CD4 T cells: alterations in tyrosine phosphorylation and loss of CD3ζ expression. Blood 97, 3851–3859 (2001).
    Article CAS Google Scholar
  18. Krishnan, S., Warke, V.G., Nambiar, M.P., Tsokos, G.C. & Farber, D.L. The FcR gamma subunit and Syk kinase replace the CD3 zeta-chain and ZAP-70 kinase in the TCR signaling complex of human effector CD4 T cells. J. Immunol. 170, 4189–4195 (2003).
    Article CAS Google Scholar
  19. Gorman, C.L. et al. Polymorphisms in the CD3Z gene influence TCRzeta expression in systemic lupus erythematosus patients and healthy controls. J. Immunol. 180, 1060–1070 (2008).
    Article CAS Google Scholar
  20. Warchol, T. et al. The CD3Z 844 T>A polymorphism within the 3′-UTR of CD3Z confers increased risk of incidence of systemic lupus erythematosus. Tissue Antigens 74, 68–72 (2009).
    Article CAS Google Scholar
  21. Gourh, P. et al. Association of the PTPN22 R620W polymorphism with anti-topoisomerase I- and anticentromere antibody-positive systemic sclerosis. Arthritis Rheum. 54, 3945–3953 (2006).
    Article CAS Google Scholar
  22. Anonymous. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 23, 581–590 (1980).
  23. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).
    Article CAS Google Scholar
  24. Tian, C. et al. European population genetic substructure: further definition of ancestry informative markers for distinguishing among diverse European ethnic groups. Mol. Med. 15, 371–383 (2009).
    Article CAS Google Scholar

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Acknowledgements

This work was supported by the following grants: T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). J.M. was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain and in part by Redes Temáticas de Investigación Cooperativa Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain (J.M.). R.B. is supported by the I3P Consejo Superior de Investigaciones Científicas program funded by the 'Fondo Social Europeo'. B.Z.A. is supported by the Netherlands Organization for Health Research and Development (ZonMW grant 016.096.121). B.K. is supported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). Genotyping of the Dutch control samples was sponsored by US National Insitutes of Mental Health funding, R01 MH078075 (R.O.A.). The German controls were from the PopGen biobank (to B.K.). The PopGen project received infrastructure support through the German Research Foundation excellence cluster 'Inflammation at Interfaces'. The US analyses were supported by the US National Institutes of Health and National Institute of Arthritis and Musculoskeletal Diseases (NIH-NIAMS) R01 AR055258, Two-Stage Genome Wide Association Study in Systemic Sclerosis, (M.D.M.) and by the NIH-NIAMS Center of Research Translation (CORT) in SSc (P50AR054144) (F.C.A.), the NIH-NIAMS SSc Family Registry and DNA Repository (N01-AR-0-2251) (M.D.M.), University of Texas Health Science Center-Houston Center for Clinical and Translational Sciences (Houston Clinical and Translational Science Awards Program) (NIH-National Center for Research Resources 3UL1RR024148) (F.C.A.), NIH-NIAMS K08 Award (K08AR054404) (S.K.A.), SSc Foundation New Investigator Award (S.K.A.).

Author information

Author notes

  1. Timothy R D J Radstake, Olga Gorlova, Blanca Rueda, Jose-Ezequiel Martin, Bobby P C Koeleman, Frank C Arnett, Javier Martin and Maureen D Mayes: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    Timothy R D J Radstake, Madelon C Vonk, Jasper C Broen & Piet L C M van Riel
  2. Department of Epidemiology, M.D. Anderson Cancer Center, Houston, Texas, USA
    Olga Gorlova, Jun Ying, Younghun Han, Shih-Feng Weng & Christopher I Amos
  3. Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain
    Blanca Rueda, Jose-Ezequiel Martin, Rogelio Palomino-Morales & Javier Martin
  4. Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
    Behrooz Z Alizadeh, Ruben van 't Slot, Annet Italiaander, Roel A Ophoff & Bobby P C Koeleman
  5. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    Marieke J Coenen
  6. Department of Rheumatology, Vrije Universiteit (VU) Medical Centre, Nijmegen, The Netherlands
    Alexandre E Voskuyl
  7. Department of Rheumatology, University of Leiden, Nijmegen, The Netherlands
    Annemie J Schuerwegh
  8. University of California Los Angeles Center for Neurobehavioral Genetics, Los Angeles, California
    Roel A Ophoff
  9. Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany
    Gabriela Riemekasten
  10. Department of Dermatology, University of Cologne, Cologne, Germany
    Nico Hunzelmann
  11. Servicio de Medicina Interna, Hospital Valle de Hebron, Barcelona, Spain
    Carmen P Simeon
  12. Servicio de Medicina Interna, Hospital Clínico Universitario, Granada, Spain
    Norberto Ortego-Centeno
  13. Servicio de Reumatología, Hospital Marqués de Valdecilla, Santander, Spain
    Miguel A González-Gay & Patricia Carreira
  14. Servicio de Inmunología, Hospital Virgen del Rocío, Sevilla, Spain
    María F González-Escribano
  15. University of Brescia, Brescia, Italy
    Paolo Airo
  16. University of Newcastle, Newcastle Upon Tyne, UK
    Jaap van Laar
  17. Department of Rheumatology and Epidemiology, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
    Ariane Herrick & Jane Worthington
  18. University of Lund, Lund, Sweden
    Roger Hesselstrand
  19. University of Ghent, Ghent, Belgium
    Vanessa Smith & Filip de Keyser
  20. University of Leuven, Leuven, Belgium
    Fredric Houssiau
  21. University of Glasgow, Glasgow, UK
    Meng May Chee, Rajan Madhok & Paul Shiels
  22. University of Antwerpen, Antwerpen, Belgium
    Rene Westhovens
  23. Ruhr University of Bochum, Bochum, Germany
    Alexander Kreuter
  24. University of Vienna, Vienna, Austria
    Hans Kiener
  25. Department of Genetics, University of Ghent, Ghent, Belgium
    Elfride de Baere
  26. University of Hannover, Hannover, Germany
    Torsten Witte
  27. Karolinska Institute, Stockholm, Sweden
    Leonid Padykov & Lars Klareskog
  28. Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy
    Lorenzo Beretta & Rafaella Scorza
  29. Institute of Immunology, Oslo University Hospital, Oslo, Norway
    Benedicte A Lie
  30. Department of Rheumatology, Rikshospitalet, Oslo University Hospital, Oslo, Norway
    Anna-Maria Hoffmann-Vold
  31. Hospital 12 de Octubre, Madrid, Spain
    Patricia Carreira
  32. Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    John Varga & Monique Hinchcliff
  33. Feinstein Institute of Medical Research, Manhasset, New York, USA
    Peter K Gregersen & Annette T Lee
  34. Johns Hopkins University Medical Center, Baltimore, Maryland, USA
    Fredrick M Wigley & Laura Hummers
  35. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
    J Lee Nelson
  36. The University of Texas Health Science Center–Houston, Houston, Texas, USA
    Sandeep K Agarwal, Shervin Assassi, Pravitt Gourh, Filemon K Tan, Frank C Arnett & Maureen D Mayes

Authors

  1. Timothy R D J Radstake
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  2. Olga Gorlova
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  3. Blanca Rueda
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  4. Jose-Ezequiel Martin
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  5. Behrooz Z Alizadeh
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  6. Rogelio Palomino-Morales
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  7. Marieke J Coenen
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  8. Madelon C Vonk
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  9. Alexandre E Voskuyl
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  10. Annemie J Schuerwegh
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  11. Jasper C Broen
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  12. Piet L C M van Riel
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  13. Ruben van 't Slot
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  14. Annet Italiaander
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  15. Roel A Ophoff
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  16. Gabriela Riemekasten
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  17. Nico Hunzelmann
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  18. Carmen P Simeon
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  19. Norberto Ortego-Centeno
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  20. Miguel A González-Gay
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  21. María F González-Escribano
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  22. Paolo Airo
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  23. Jaap van Laar
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  24. Ariane Herrick
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  25. Jane Worthington
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  26. Roger Hesselstrand
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  27. Vanessa Smith
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  28. Filip de Keyser
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  29. Fredric Houssiau
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  30. Meng May Chee
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  31. Rajan Madhok
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  32. Paul Shiels
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  33. Rene Westhovens
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  34. Alexander Kreuter
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  35. Hans Kiener
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  36. Elfride de Baere
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  37. Torsten Witte
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  38. Leonid Padykov
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  39. Lars Klareskog
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  40. Lorenzo Beretta
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  41. Rafaella Scorza
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  42. Benedicte A Lie
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  43. Anna-Maria Hoffmann-Vold
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  44. Patricia Carreira
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  45. John Varga
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  46. Monique Hinchcliff
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  47. Peter K Gregersen
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  48. Annette T Lee
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  49. Jun Ying
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  50. Younghun Han
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  51. Shih-Feng Weng
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  52. Christopher I Amos
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  53. Fredrick M Wigley
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  54. Laura Hummers
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  55. J Lee Nelson
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  56. Sandeep K Agarwal
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  57. Shervin Assassi
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  58. Pravitt Gourh
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  59. Filemon K Tan
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  60. Bobby P C Koeleman
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  61. Frank C Arnett
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  62. Javier Martin
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  63. Maureen D Mayes
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Consortia

Spanish Scleroderma Group

Contributions

Study Design: T.R.D.J.R., O.G., B.R., J.-E.M., B.P.C.K., F.C.A., J.M., M.D.M.

Collection of data: T.R.D.J.R., M.J.C., M.C.V., A.E.V., A.J.S., J.C.B., B.A.L., A.-M.H.-V., R.A.O., G.R., N.H., C.P.S., N.O.-C., M.A.G.-G., M.F.G.-E., P.A., J.v.L., A.H., J.W., R.H., V.S., F.d.K., F.H., M.M.C., R.M., P.S., R.W., A.K., H.K., E.d.B., T.W., L.P., L.K., L.B., R.S., J.V., M.H., P.G., J.L.N., F.M.W., L.H., P.C., S.A.

Interpretation and analysis of results: T.R.D.J.R., O.G., B.R., J.-E.M., B.Z.A., R.P.-M., J.Y., Y.H., S.-F.W., R.v.'t.S., P.G., A.T.L., C.I.A., S.K.A., B.P.C.K., J.M., M.D.M., A.I., P.C., S.A., P.K.G.

Critical reading of manuscript: T.R.D.J.R., O.G., B.R., J.-E.M., B.Z.A., J.Y., M.J.C., M.C.V., A.E.V., A.J.S., J.C.B., P.L.C.M.v.R., R.v.S., B.A.L., A.-M.H.-V., G.R., N.H., C.P.S., N.O.-C., M.A.G.-G., M.F.G.-E., P.A., J.v.L., A.H., J.W., R.H., V.S., F.d.K., F.H., M.M.C., R.M., P.S., R.W., A.K., H.K., E.d.B., T.W., L.P., L.B., R.S., J.V., M.H., P.G., C.I.A., J.L.N., F.M.W., L.H., S.K.A., P.G., F.K.T., B.P.C.K., F.C.A., J.M., M.D.M., P.K.G.

Project conception: T.R.D.J.R., B.P.C.K., F.C.A., J.M., M.D.M.

Corresponding authors

Correspondence toTimothy R D J Radstake or Maureen D Mayes.

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The authors declare no competing financial interests.

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A full list of members is provided in the Supplementary Note.

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Radstake, T., Gorlova, O., Rueda, B. et al. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus.Nat Genet 42, 426–429 (2010). https://doi.org/10.1038/ng.565

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