THU0005 An immunochip based interrogation of scleroderma susceptibility variants

Background Understanding the genetic architecture of scleroderma (SSc) susceptibility is vital both in gene discovery and in determining the influence of previous identified susceptibility variants. Objectives To perform an immunochip-based interrogation of scleroderma susceptibility variants using cases from the Australian Scleroderma Cohort Study. Methods We selected 557 cases from the Australian Scleroderma Cohort Study for genotyping with the Immunochip, a custom Illumina Infinium genotyping array containing 196,524 rare and common variants shown to be important in a wide variety of autoimmune disorders. 4,537 controls were taken from the 1958 British Birth cohort. Genotype data were analysed with PLINK. Samples and SNPs with low call rates were excluded, as were SNPs in Hardy-Weinberg disequilibrium or with less than two occurrences of the minor allele. Eigenstrat was used to analyze population structure. The final dataset consisted of 505 cases, 4,491 controls and 146,867 SNPs. Allelic association analyses were conducted using Fisher’s exact test. Genotype clusters were manually examined for all associations of p