Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

Genome-Wide Association Study in Systemic Sclerosis.

Allanore5,  Yannick, Saad2,  Mohammad, Dieude4,  Philippe, Boileau1,  Catherine, Martinez3,  Maria, GENESYS Consortium,  

Biochimie A. Paré Hospital, Université VSQ, Boulogne, France
INSERM U563 Université Paul Sabatier, Toulouse, France
NSERM U563 Université Paul Sabatier, Toulouse, France
Rhumatologie, Inserm u699, Bichat, Paris Diderot Universite, France
Université Paris Descarte, Rhumatologie A, INSERM U781, Paris, Paris, France

Systemic sclerosis (SSc) is an orphan multi-organ disease affecting the immune system, the microvascular network and the connective tissue. SSc leads to major disability and premature death. Epidemiological data suggest a complex genetic etiology.

To dissect genetic susceptibility to SSc we have performed a genome-wide association study in 654 SSc patients of French Caucasian origin from the GENESYS study, and 2,543 French controls (subjects without SSc from GENESYS project and neurologically healthy subjects from the Three-City cohort- Lambert et al, Nat Genet. 2009;41:1094–9). Subjects were genotyped using the Illumina Human 610 QUAD bead chip. The final post-QC discovery (stage-1) sample comprised 564 SSc cases and 2,466 controls, and a total of 489,814 SNPs passed quality control criteria. Association was tested using logistic regression assuming additive genetic effects and adjusted for the two principal components to account for population substructure. The genome-wide association results revealed a number of SNPs with strong evidence (P<10-5) of association. Interestingly, in our discovery sample, stronger signals were detected for 6 non-HLA SNPs that spanned 5 distinct genomic loci. Two SNPs belong to a candidate gene previously reported associated to other autoimmune disease of high relevance with regards to SSc pathogenesis. Furthermore, the remaining 4 SNPs are located on 3 previously unreported putative SSc loci. 2 SNPs are close to genes coding for neuro-mediators and 1 SNP is close to a metabolic gene recently showed to deeply contribute to extra-cellular matrix remodeling. Follow-up and replication analysis (stage-2) of these promising and new association signals are under way in a second French/Italian/German/Eastern case-control sample (>1,750 SSc cases and 3,200 controls). Our preliminary GWAS results identified a tractable number of novel candidate genes for SSc that warrant further investigation. All top best associated SNPs will be reported in the meeting.

This work was supported by French, German and Italian research networks on systemic sclerosis and by ANR grant (Projet R08160KS), Association des Sclérodermies de France, Research grants from Institut Servier and Sanofi Aventis, France.

To cite this abstract, please use the following information:
Allanore, Yannick, Saad, Mohammad, Dieude, Philippe, Boileau, Catherine, Martinez, Maria, GENESYS Consortium, ; Genome-Wide Association Study in Systemic Sclerosis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1994
DOI: 10.1002/art.29759

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