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Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus

A Corrigendum to this article was published on 27 April 2011

This article has been updated


Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls. Analysis of 279,621 autosomal SNPs followed by replication testing in an independent case-control set of European ancestry (2,753 individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22–23, rs2056626, P = 2.09 × 10−7 in the discovery samples, P = 3.39 × 10−9 in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 × 10−18), IRF5 (P = 1.86 × 10−13) and STAT4 (P = 3.37 × 10−9) gene regions as SSc genetic risk factors.

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Figure 1: Manhattan plot of the GWAS of the discovery cohort comprising 2,346 SSc cases and 5,193 healthy controls.
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Change history

  • 16 April 2010

    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.

  • 23 March 2011

    In the version of this article initially published, incorrect affiliations were published for Lorenzo Beretta and Raffaella Scorza. The correct affiliation for Lorenzo Beretta and Raffaella Scorza is "Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan". The error has been corrected in the HTML and PDF versions of the article.


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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.).

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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 to Timothy 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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Supplementary Tables 1–5, Supplementary Figures 1–4 and Supplementary Note (PDF 2108 kb)

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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).

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