Type 1 diabetes (T1D) is a common autoimmune disorder with some genetic basis. T1D patients often suffer from additional autoimmune conditions, such as rheumatoid arthritis. This study identifies genes that confer risk for T1D, and finds some overlap between genetic risk profiles for T1D and other autoimmune disorders.

ABSTRACT

Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10(-8)). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34(+) stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal.

Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.

Onengut-Gumuscu S, Chen WM, Burren O, Cooper NJ, Quinlan AR, Mychaleckyj JC, Farber E, Bonnie JK, Szpak M, Schofield E, Achuthan P, Guo H, Fortune MD, Stevens H, Walker NM, Ward LD, Kundaje A, Kellis M, Daly MJ, Barrett JC, Cooper JD, Deloukas P; Type 1 Diabetes Genetics Consortium, Todd JA,Wallace C, Concannon P, Rich SS.

Nat Genet. 2015 Apr;47(4):381-6. doi: 10.1038/ng.3245. Epub 2015 Mar 9.

PMID: 25751624 [PubMed - indexed for MEDLINE] PMCID: PMC4380767 [Available on 2015-10-01]

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