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Genetics of coronary artery disease in the 21st century

Robert Roberts1, Alexandre F R Stewart

  • 1John and Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Canada. rroberts@ottawaheart.ca

Clinical Cardiology
|May 17, 2012
PubMed

Insights

Coronary artery disease (CAD) is preventable by managing genetic and environmental risk factors. Genome-wide studies reveal numerous genetic variants contributing to CAD, many independent of traditional risk factors, highlighting new prevention and treatment avenues.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Preventive Cardiology

Background:

  • Coronary artery disease (CAD) remains the leading global cause of mortality.
  • Clinical evidence shows that addressing known risk factors can reduce CAD mortality and morbidity by 30-40%.
  • Genetic predisposition is estimated to contribute up to 50% of an individual's susceptibility to CAD.

Purpose of the Study:

  • To explore the role of genetic and environmental factors in CAD prevention.
  • To identify novel genetic risk variants for CAD through genome-wide association studies (GWAS).
  • To understand the contribution of these variants to CAD pathogenesis, particularly those independent of conventional risk factors.

Main Methods:

  • Utilized genome-wide association studies (GWAS) to identify genetic variants associated with CAD.
  • Validated identified genetic variants for genome-wide significance (P < 5 × 10(-8)) and replication in independent populations.
  • Analyzed the prevalence of identified risk variants within the general population.

Main Results:

  • Identified 36 genetic variants significantly associated with increased CAD risk.
  • Over 50% of these variants are present in more than 50% of the population, with 10 variants found in over 75%.
  • Crucially, over 66% of these risk variants do not act through established conventional risk factors, suggesting novel pathogenic mechanisms.

Conclusions:

  • Genetic predisposition plays a significant role in CAD, conferred by common DNA variants.
  • A substantial portion of CAD pathogenesis involves factors yet to be fully determined, beyond traditional risk factors.
  • Comprehensive CAD prevention strategies must integrate the management of both genetic and environmental risk factors, with genetic screening and targeted therapies on the horizon.

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