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

Journal article

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.

Authors: Maller, J; McVean, G; Byrnes, J; Vukcevic, D; Palin, K

• Publication status: Published
• Journal: Nature genetics
• Volume: 44
• Issue: 12
• Pages: 1294-1301
• Publication date: 2012-12-01
• DOI: 10.1038/ng.2435
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Humans; Diabetes Mellitus, Type 2; Polymorphism, Single Nucleotide; Proteins; Transcription Factor 7-Like 2 Protein; Genome-Wide Association Study; Genetic Loci; Genetic Predisposition to Disease; Transcription Factors; Wellcome Trust Case Control Consortium; Cyclin-Dependent Kinase Inhibitor p15; Coronary Artery Disease; CTLA-4 Antigen; Homeodomain Proteins; Graves Disease; Cyclin-Dependent Kinase 5; Genes, p16; Bayes Theorem