TY - JOUR
T1 - Bayesian refinement of association signals for 14 loci in 3 common diseases
AU - Wellcome Trust Case Control Consortium
AU - Maller, Julian B
AU - McVean, Gilean
AU - Byrnes, Jake
AU - Vukcevic, Damjan
AU - Palin, Kimmo
AU - Su, Zhan
AU - Howson, Joanna M M
AU - Auton, Adam
AU - Myers, Simon
AU - Morris, Andrew
AU - Pirinen, Matti
AU - Brown, Matthew A
AU - Burton, Paul R
AU - Caulfield, Mark J
AU - Compston, Alastair
AU - Farrall, Martin
AU - Hall, Alistair S
AU - Hattersley, Andrew T
AU - Hill, Adrian V S
AU - Mathew, Christopher G
AU - Pembrey, Marcus
AU - Satsangi, Jack
AU - Stratton, Michael R
AU - Worthington, Jane
AU - Craddock, Nick
AU - Hurles, Matthew
AU - Ouwehand, Willem
AU - Parkes, Miles
AU - Rahman, Nazneen
AU - Duncanson, Audrey
AU - Todd, John A
AU - Kwiatkowski, Dominic P
AU - Samani, Nilesh J
AU - Gough, Stephen C L
AU - McCarthy, Mark I
AU - Deloukas, Panagiotis
AU - Donnelly, Peter
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Bayes Theorem
KW - CTLA-4 Antigen
KW - Coronary Artery Disease
KW - Cyclin-Dependent Kinase 5
KW - Cyclin-Dependent Kinase Inhibitor p15
KW - Diabetes Mellitus, Type 2
KW - Genes, p16
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Graves Disease
KW - Homeodomain Proteins
KW - Humans
KW - Polymorphism, Single Nucleotide
KW - Proteins
KW - Transcription Factor 7-Like 2 Protein
KW - Transcription Factors
U2 - 10.1038/ng.2435
DO - 10.1038/ng.2435
M3 - Article
C2 - 23104008
SN - 1061-4036
VL - 44
SP - 1294
EP - 1301
JO - Nature Genetics
JF - Nature Genetics
ER -