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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-04

AUTHORS

Suna Onengut-Gumuscu, Wei-Min Chen, Oliver Burren, Nick J Cooper, Aaron R Quinlan, Josyf C Mychaleckyj, Emily Farber, Jessica K Bonnie, Michal Szpak, Ellen Schofield, Premanand Achuthan, Hui Guo, Mary D Fortune, Helen Stevens, Neil M Walker, Lucas D Ward, Anshul Kundaje, Manolis Kellis, Mark J Daly, Jeffrey C Barrett, Jason D Cooper, Panos Deloukas, Type 1 Diabetes Genetics Consortium, John A Todd, Chris Wallace, Patrick Concannon, Stephen S Rich

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. More... »

PAGES

381-386

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3245

    DOI

    http://dx.doi.org/10.1038/ng.3245

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1023215740

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25751624


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