Genetics of coronary artery disease: Genome-wide association studies and beyond

Bram P. Prins, Vasiliki Lagou, Folkert W. Asselbergs, Harold Snieder*, Jingyuan Fu

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Genome-wide association (GWA) studies on coronary artery disease (CAD) have been very successful, identifying a total of 32 susceptibility loci so far. Although these loci have provided valuable insights into the etiology of CAD, their cumulative effect explains surprisingly little of the total CAD heritability. In this review, we first highlight and describe the type of genetic variants potentially underlying the missing heritability of CAD: single nucleotide polymorphisms (SNPs) or structural variants, each ofwhich may either be common or rare. Although finding missing heritability is important, we further argue in this review that it constitutes only a first step towards a fuller understanding of the etiology of CAD development. To close the gap between the genotype and phenotype, we propose a systems genetics approach in the post-GWA study era. This approach that integrates genetic, epigenetic, transcriptomic, proteomic, metabolic and intermediate outcome variables has potential to significantly aid the understanding of CAD etiology. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalATHEROSCLEROSIS
Volume225
Issue number1
DOIs
Publication statusPublished - Nov-2012

Keywords

  • Heritability
  • Coronary artery disease
  • Genome-wide association study
  • Systems genetics
  • SINGLE-NUCLEOTIDE POLYMORPHISMS
  • 2-LOCUS LINKAGE ANALYSIS
  • MYOCARDIAL-INFARCTION
  • HEART-DISEASE
  • RARE VARIANTS
  • CARDIOVASCULAR-DISEASE
  • MISSING HERITABILITY
  • COMPLEX DISEASES
  • SUSCEPTIBILITY LOCUS
  • LP(A) LIPOPROTEIN

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