A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
John F. Pedena b c, Martin Farralla b c, Anuj Goela b d, Halit Ongena b e, Anna Helgadóttira b, Shapour Jalilzadeha b, Theodosios Kyriakoua b c, Peter Sleightb d, Jemma C. Hopewelle f, Rory Collinsc f✉, Sarah Parishf, Robert Clarkee f, Alison R. Offerf g h, Louise Bowmanc f, Jane Armitagef, Richard Petoc f, Pamela Linkstedc f, Derrick Bennettf, Danish Saleheene i j✉, Asif Rasheedc i, Moazzam Ali Zaidic i, Nabi Shahg h i, Maria Samuei, Philippe M. Frossardg h i, John Daneshc j, John Campbell Chambersg h k l, Paul Elliottl m, Weihua Zhangk l, Jaspal Singh Koonerk n✉, Jörg Hagero and 71 others
- aDepartment of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
- bDepartment of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK
- cUniversity of Oxford, Oxford, United Kingdom
- dUniversity of Cambridge, Cambridge, United Kingdom
- eImperial College London, London, United Kingdom
- fClinical Trial Service Unit, University of Oxford, Oxford, UK
- gKarolinska Institutet, Stockholm, Sweden
- hKarolinska University Hospital, Stockholm, Sweden
- iCenter for Non-Communicable Diseases Pakistan, Karachi, Pakistan
- jDepartment of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
- kCardiology, Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK
- l
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Abstract
Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)¹⁻⁷, a modest number considering the apparent heritability of CAD⁸. All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with ∼575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 × 10⁻⁸ in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
TL;DRA meta-analysis of four large genome-wide association studies of CAD found a CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects, implicate new pathways for CAD susceptibility. (Semantic Scholar)