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OP0282 New systemic sclerosis risk loci identified through a meta-gwas strategy
  1. E. López-Isac1,
  2. M. Acosta-Herrera1,
  3. S. Assassi2,
  4. C.P. Simeón1,
  5. P.E. Carreira1,
  6. I. Castellví1,
  7. N. Ortego-Centeno1,
  8. L. Beretta3,
  9. C. Lunardi4,
  10. A. Gabrielli5,
  11. G. Moroncini5,
  12. N. Hunzelmann6,
  13. T. Witte7,
  14. J.H. Distler8,
  15. A. Franke9,
  16. A.E. Voskuyl10,
  17. J. de Vries-Bouwstra11,
  18. C. Wijmenga12,
  19. R. Hesselstrand13,
  20. A. Nordin14,
  21. A.-M. Hoffmann-Vold15,
  22. A. Herrick16,
  23. J. Worthington16,
  24. C.P. Denton17,
  25. M.A. Brown18,
  26. on behalf of Australian Scleroderma Interest Group,
  27. Y. Allanore19,
  28. on behalf of French GENESYS Consortium,
  29. T.R. Radstake20,
  30. C. Fonseca17,
  31. M.D. Mayes21,
  32. J. Martín1,
  33. on behalf of Spanish Scleroderma Group
  1. 1Instituto de Parasitología y Biomedicina López Neyra (CSIC)., Granada, Spain
  2. 2The University of Texas Health Science Center–Houston, Houston, Texas, USA
  3. 3Referral Center for Systemic Autoimmune Diseases, Milan
  4. 4Università degli Studi di Verona, Verona
  5. 5Università Politecnica delle Marche and Ospedali Riuniti, Ancona, Italy
  6. 6Cologne University, Cologne
  7. 7Hannover Medical School, Hannover
  8. 8University of Erlangen-Nuremberg, Erlangen
  9. 9Christian-Albrechts-University of Kiel, Kiel, Germany
  10. 10VU University Medical Center, Amsterdam
  11. 11Leiden University Medical Center, Leiden
  12. 12University Medical Center Groningen, Groningen, Netherlands
  13. 13Lund University, Lund
  14. 14Karolinska Institute, Stockholm, Sweden
  15. 15Oslo University Hospital, Oslo, Norway
  16. 16The University of Manchester, Manchester
  17. 17Royal Free and University College Medical School, London, UK
  18. 18University of Queensland Diamantina Institute, Queensland, Australia
  19. 19Paris Descartes University, Paris, France
  20. 20University Medical Center Utrecht, Utrecht, Netherlands
  21. 21The University of Texas Health Science Center–Houston, Housron, Texas, USA


Background In systemic sclerosis (SSc), previous GWASs have identified several loci associated with the disease, but their rate of discovery has been limited due to modest sample sizes. Extensive collaborative efforts have enabled us to gather the largest cohort of SSc patients. In the present study, we have performed a large meta-GWAS taking advantage of our well-powered cohort.

Objectives To continue unravelling the complex genetic component of SSc.

Methods The complete set of individuals enrolled for this study comprised a total of 26 679 genome-wide genotyped individuals of European ancestry. PLINK and EIGENSTRAT were used for quality control and population stratification adjustments. Genotype imputation was performed with IMPUTE2 and the 1000 Genome Project Phase 3 as reference panel.

Results Twenty-three loci reached the genome-wide significance level (p-value<5×10–8) in our large-scale meta-analysis. Twelve out of the total significant signals represented new associations and involved novel pathways in the pathophysiology of the disease. Significant enrichment was observed for epigenetic marks of active promoters and active enhancers in critical cell types for the disease. In addition many of the interrogated variants correlated with eQTLs thus altering gene expression.

Conclusions Using a large meta-GWAS, we have identified twelve novel associations for SSc susceptibility and confirmed several previously reported risk loci. These results considerably increase our understanding of the genetic basis of SSc and shed light on the pathogenesis of the disease providing important information to discover new therapeutic targets genetically validated.

Disclosure of Interest None declared

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