Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers
Details
Publication Year 2015-04, Volume 47, Issue #4, Page 381-6
Journal Title
Nature Genetics
Publication Type
Journal Article
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 x 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.
Publisher
NPG
WEHI Research Division(s)
Population Health And Immunity
PubMed ID
25751624
Publisher's Version
https://doi.org/10.1038/ng.3245
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2016-02-29 12:20:49
Last Modified: 2019-04-01 09:04:32
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