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

Nat Genet. 2011 Mar 6;43(4):339-44. doi: 10.1038/ng.782.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAMTS7 Protein
  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics
  • Case-Control Studies
  • Coronary Artery Disease / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Lymphokines / genetics
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Platelet-Derived Growth Factor / genetics
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Sterol Esterase / genetics
  • Transcription Factors / genetics

Substances

  • Lymphokines
  • MORF4L1 protein, human
  • PDGFD protein, human
  • Platelet-Derived Growth Factor
  • Transcription Factors
  • LIPA protein, human
  • Sterol Esterase
  • ADAM Proteins
  • ADAMTS7 Protein
  • ADAMTS7 protein, human