The genetics of scleroderma: looking into the postgenomic era

The last decade has seen enormous progress in understanding genetic associations of systemic sclerosis to explain the observed heritability. This review highlights the most recent findings and places them in the context of proposed functional roles.

Over 30 genes and gene regions have now been identified as scleroderma susceptibility loci. These include both human leukocyte antigen (HLA) and non-HLA genes, most of which involve immune-related pathways and modifiers of immune function. Many of these associations have also been reported in other systemic autoimmune diseases and suggest that there are multiple autoimmunity genes resulting in disease occurrence.

In spite of these advances, only a small proportion of the heritability of systemic sclerosis has been explained. Ongoing studies include fine mapping and sequencing studies to identify causal variants, whereas other studies focus on functional consequences of these variants in order to identify the link between these genetic variants and disease susceptibility. Such knowledge should lead to more targeted and effective treatment in this disease.