Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Identification of Novel Genes Associated with Systemic Sclerosis Through Genome Wide Association Study Follow-up.

Martin1,  Jose Ezequiel, Broen2,  Jasper, Gorlova3,  Olga Y., Vonk4,  Madelon C., Spanish Scleroderma Group,  , Voskuyl6,  Alexandre, Schuerwegh7,  Annemie

Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Armilla (Granada), Spain
University Hospital KU Leuven, Leuven, Belgium
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
Ruhr University Bochum, Bochum, Germany
Charité University Hospital, German Rheumatology Research Center, a Leibniz Institute, Berlin, Germany
Lund University & Skåne University Hopsital, Lund, Sweden
Karolinska Institute, Stockholm, Sweden
Rikshospitalet, Oslo University Hospital, Oslo, Norway
Brescia, Italy
University of Cologne, Cologne, Germany
IRCCS Fondazione Policlinico-Mangiagalli-Regina Elena & University of Milan, Milan, Italy
Radboud University Nijmegen Medical Centre, Nijmegen, Nijmegen, Netherlands
University of Texas Health Science Center at Houston, Houston, TX
Geert Groote Plein 8, Nymegen, Netherlands
Instituto de Parasitologia y Biomedicina Lopez-Neyra (CSIC), Granada, Spain
University Medical Center Utrecht, Utrecht, Netherlands
UT M. D. Anderson Cancer Center, Houston, TX
Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
VU University Medical Center, Amsterdam, Netherlands
Leids Univ Medisch Centrum, Leiden, Netherlands
Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
Department of Rheumatology, Ghent University Hospital, Ghent, Belgium


Systemic sclerosis (SSc) is complex autoimmune disease affecting the connective tissue; influenced by genetic and environmental components. Recently, we performed the first successful GWAS of SSc. Here, we perform a large replication study to better dissect the genetic component of SSc.


We selected 768 polymorphisms from the previous GWAS carried out in Caucasian individuals from Europe and US; and genotyped them in nine replication cohorts from Europe. Overall significance was calculated for replicated significant SNPs by meta-analysis of the replication cohorts and replication-GWAS cohorts (3,790 cases and 6,831 controls). Finally, we searched for differential association in the main SSc subgroups of limited (lcSSc) and diffuse (dcSSc) subtypes, and auto-antibody positive for anti-centromere (ACA) and anti-topoisomerase I (ATA).


We found evidence for replication and overall genome wide significance for one novel SSc genetic risk locus: PSD3 (P value = 5.38×10-8, OR = 1.451). Additionally, we found suggestive association in the loci TMEM163 (P value = 4.50×10-7, OR = 1.169) and ADAMTS17 in the ATA+ subgroup (P value = 4.95×10-7, OR = 1.392). As expected we strengthened the evidence for previously confirmed associations in the CD247, STAT4, TNFAIP3, TNPO3/IRF5 and IRF8 loci. Additionally, we shed new light on the association of IRF5 with SSc, which suggests that this is a shared genetic risk factor with systemic lupus erythematosus.


This study significantly increases the number of known putative genetic risk factors for SSc, including the genes PSD3, TMEM163 and ADAMTS17, and further confirms five previously described ones.

To cite this abstract, please use the following information:
Martin, Jose Ezequiel, Broen, Jasper, Gorlova, Olga Y., Vonk, Madelon C., Spanish Scleroderma Group, , Voskuyl, Alexandre, et al; Identification of Novel Genes Associated with Systemic Sclerosis Through Genome Wide Association Study Follow-up. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1497

Abstract Supplement

Meeting Menu