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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.

Original publication

DOI

10.1038/ng.3245

Type

Journal article

Journal

Nat Genet

Publication Date

04/2015

Volume

47

Pages

381 - 386

Keywords

Autoantibodies, Autoimmunity, Case-Control Studies, Chromosome Mapping, DNA Mutational Analysis, Diabetes Mellitus, Type 1, Enhancer Elements, Genetic, Female, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Humans, Lymphocytes, Male, Polymorphism, Single Nucleotide