期刊
NATURE GENETICS
卷 47, 期 4, 页码 381-U199出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3245
关键词
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资金
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Human Genome Research Institute (NHGRI)
- National Institute of Child Health and Human Development (NICHD)
- US National Institutes of Health [U01 DK062418]
- NIDDK [DK046635, DK085678]
- joint JDRF
- Wellcome Trust [WT061858/09115, 089989]
- NIHR Cambridge Biomedical Research Centre
- Eli Lilly and Company
- Wellcome Trust Strategic Award [100140]
- UK Medical Research Council
- Wellcome Trust award [076113]
- MRC [G1001799, MR/N01104X/1, MC_U105261167] Funding Source: UKRI
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0644282] Funding Source: National Science Foundation
- Medical Research Council [MR/N01104X/1, G1001799, MC_U105261167] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10143, NF-SI-0513-10012, NF-SI-0508-10274, NF-SI-0508-10275] Funding Source: researchfish
Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions(1,2), finding major pathways contributing to risk(3), with some loci shared across immune disorders(4-6). 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.
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