Study population

Two non-Hispanic white populations (discovery and replication cohorts) were investigated. For the discovery cohort, we utilized data from our previously published SSc GWAS study consisting of 1486 SSc cases (patients from the US) and 3477 unaffected race- and ethnicity-matched controls [9]. Selected polymorphisms were genotyped in an independent replication cohort consisting of 1085 additional SSc cases (patients from the US and Canada) and 1023 additional unaffected controls. Patients were recruited at the University of Texas – Houston and from the following sites: the participating Canadian Scleroderma Research Group (CSRG) sites, University of California Los Angeles, University of Michigan, Georgetown University, Boston University, Medical University of South Carolina, Johns Hopkins University, University of Utah, Northwestern University, University of Alabama at Birmingham and University of Minnesota. All patients were enrolled in the National Scleroderma Family Registry and DNA Repository. All patients with SSc fulfilled the 1980 American College of Rheumatology classification criteria for SSc or had at least three of the five CREST (Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasias) features (Table 1).

Demographic and clinical features of SSc patients in the discovery and replication cohorts

ACA anti-centromere antibody, ATA anti-topoisomerase 1 antibody, SSc systemic sclerosis, ILD interstitial lung disease

The genotypes of unaffected controls for the discovery cohort were obtained from the Cancer Genetic Markers of Susceptibility (CGEMS; non-cancer healthy controls) studies and Illumina iControlDB database (www.illumina.com/iControlDB, Illumina, San Diego, CA, USA). The unaffected controls for the replication cohort were recruited through a nationwide effort by the Scleroderma Family Registry and DNA Repository.

Collection of blood samples and clinical information from case and control subjects was undertaken with fully informed consent and relevant ethical review board approval from each contributing center in accordance with the tenets of the Declaration of Helsinki.