SP0058 Fine-Mapping Causal Genetic Alleles in Rheumatoid Arthritis and Type I Diabetes
2015
Rheumatoid arthritis and Type I Diabetes are autoimmune disease causing a disabling inflammatory polyarthritis that is the result of complex genetic and environmental factors. Genetic studies have now defined >100 loci for these diseases outside of the major histocompatability complex. Only a handful of these loci implicate coding variation. Because of the difficulty in characterizing non-coding variation, investigators have only in rare instances mapped RA loci to causal alleles. This is a critical bottleneck in linking genetic risk factors to underlying disease mechanisms. If we could define causal alleles it might become possible to identify disease mechanisms, and then we might be better able to target disease therapeutically and to define biomarkers that track with disease activity. Here we first demonstrate that rheumatoid arthritis and type I diabetes risk alleles overlap gene regulatory regions specifically in CD4+ effector and 885 regulatory T cells. We then go on to lay out a fine-mapping strategy based on these results to identify causal variation within 55 Autoimmune disease loci. Disclosure of Interest None declared
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