Bayesian refinement of association signals for 14 loci in 3 common diseases

Maller, J. B., McVean, G., Byrnes, J., Vukcevic, D., Palin, K., Su, Z., Howson, J. M. M., Auton, A., Myers, S., Morris, A., Pirinen, M., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Craddock, N., Hurles, M., Ouwehand, W., Parkes, M., Rahman, N., Duncanson, A., Todd, J. A., Kwiatkowski, D. P., Samani, N. J., Gough, S. C. L., McCarthy, M. I., Deloukas, P., & Donnelly, P. (2012) Bayesian refinement of association signals for 14 loci in 3 common diseases. Nature Genetics, 44(12), pp. 1294-1301.

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To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies. © 2012 Nature America, Inc. All rights reserved.

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ID Code: 87604
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :45 Export Date: 21 September 2015 CODEN: NGENE Correspondence Address: Donnelly, P.; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; email:
Keywords: cyclin dependent kinase 5, cyclin dependent kinase inhibitor 2A, cyclin dependent kinase inhibitor 2B, cytotoxic T lymphocyte antigen 4, interleukin 2 receptor alpha, sortilin, stromal cell derived factor 1, transcription factor 7 like 2, article, Bayes theorem, CDKAL1 gene, chromosome 1q, chromosome 2q, controlled study, coronary artery disease, FCRL3 gene, FTO gene, gene, gene function, gene locus, gene mapping, genetic association, genetic susceptibility, genotype, Graves disease, homeobox, human, IL2RA gene, JAZF1 gene, non insulin dependent diabetes mellitus, priority journal, single nucleotide polymorphism, CTLA-4 Antigen, Cyclin-Dependent Kinase 5, Cyclin-Dependent Kinase Inhibitor p15, Diabetes Mellitus, Type 2, Genes, p16, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeodomain Proteins, Humans, Polymorphism, Single Nucleotide, Proteins, Transcription Factor 7-Like 2 Protein, Transcription Factors
DOI: 10.1038/ng.2435
ISSN: 10614036 (ISSN)
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Nature Publishing Group
Deposited On: 21 Sep 2015 06:39
Last Modified: 23 Sep 2015 04:40

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