The Genetics of Scleroderma

Systemic sclerosis (SSc) or scleroderma is a multisystem, autoimmune disorder characterised by progressive vascular, inflammatory and fibrotic dysfunction, manifesting initially as Raynaud's phenomenon and skin thickening. The visceral complications of cardiac, pulmonary, gastro-intestinal, muscle and renal disease can have devastating effects on quality of life and life-expectancy.

It is postulated that SSc develops in genetically predisposed individuals who encounter environmental or other stochastic factors. Familial SSc has been reported and other studies have confirmed that a family history of SSc is the strongest known risk for developing the disorder. Scleroderma has a well-established genetic component. To date candidate gene and genome-wide association studies have identified several genome-wide significant SSc susceptibility loci, with several more regions requiring replication.

Understanding the genetic architecture of scleroderma (SSc) susceptibility is vital both in gene discovery and in determining the influence of previous identified susceptibility variants. To identify further susceptibility loci and to explore the genetic overlap with other antibody-mediated immune diseases, we have initiated a pilot SSc association study using the Immunochip. This custom Illumina Infinium genotyping array contains 195,806 common and rare SNPs of interest in a wide variety of autoimmune disorders. It includes dense coverage of established genome-wide significant autoimmune loci for fine-mapping, and lower density coverage of loci not yet confirmed as genome-wide significant for replication.

To date, this pilot study has confirmed previously reported SSc associations, revealed further genetic overlap between SSc and lupus, and identified putative novel SSc susceptibility loci including a rare allele with major effect size.

Research Groups

Related Diseases


Team Leaders

  • Dr Jac Charlesworth