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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-12

AUTHORS

The Wellcome Trust Case Control Consortium, Julian B Maller, Gilean McVean, Jake Byrnes, Damjan Vukcevic, Kimmo Palin, Zhan Su, Joanna M M Howson, Adam Auton, Simon Myers, Andrew Morris, Matti Pirinen, Matthew A Brown, Paul R Burton, Mark J Caulfield, Alastair Compston, Martin Farrall, Alistair S Hall, Andrew T Hattersley, Adrian V S Hill, Christopher G Mathew, Marcus Pembrey, Jack Satsangi, Michael R Stratton, Jane Worthington, Nick Craddock, Matthew Hurles, Willem Ouwehand, Miles Parkes, Nazneen Rahman, Audrey Duncanson, John A Todd, Dominic P Kwiatkowski, Nilesh J Samani, Stephen C L Gough, Mark I McCarthy, Panagiotis Deloukas, Peter Donnelly

ABSTRACT

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. More... »

PAGES

1294

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.2435

DOI

http://dx.doi.org/10.1038/ng.2435

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016174016

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23104008


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503 schema:name The Wellcome Trust, Gibbs Building, London, UK.
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505 https://www.grid.ac/institutes/grid.5335.0 schema:alternateName University of Cambridge
506 schema:name Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
507 Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
508 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
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511 schema:name Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, UK.
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513 https://www.grid.ac/institutes/grid.5600.3 schema:alternateName Cardiff University
514 schema:name Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
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517 schema:name Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK.
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519 https://www.grid.ac/institutes/grid.8391.3 schema:alternateName University of Exeter
520 schema:name Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
521 Genetics of Diabetes, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
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523 https://www.grid.ac/institutes/grid.9909.9 schema:alternateName University of Leeds
524 schema:name Multidisciplinary Cardiovascular Research Centre (MCRC), Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds, UK.
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526 https://www.grid.ac/institutes/grid.9918.9 schema:alternateName University of Leicester
527 schema:name Department of Genetics, University of Leicester, Leicester, UK.
528 Department of Health Sciences, University of Leicester, Leicester, UK.
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