A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease.

John F. Peden, Jemma C. Hopewell, Danish Saleheen, John C. Chambers, Jorg Hager, Nicole Soranzo, Rory Collins, John Danesh, Paul Elliott, Martin Farrall, Kathleen E. Stirrups, Weihua Zhang, Sarah Parish, Anders Hamsten, Mark Lathrop, Hugh Watkins, Robert Clarke, Panos Deloukas, Jaspal Singh Kooner, Nabi Shah

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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.
Original languageEnglish
Pages (from-to)339-344
Number of pages7
JournalNature Genetics
Volume43
Issue number4
Publication statusPublished - 6 Mar 2011

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    Peden, J. F., Hopewell, J. C., Saleheen, D., Chambers, J. C., Hager, J., Soranzo, N., Collins, R., Danesh, J., Elliott, P., Farrall, M., Stirrups, K. E., Zhang, W., Parish, S., Hamsten, A., Lathrop, M., Watkins, H., Clarke, R., Deloukas, P., Kooner, J. S., & Shah, N. (2011). A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nature Genetics, 43(4), 339-344. https://www.nature.com/articles/ng.782#author-information