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A Journey through Genetic Architecture and Predisposition of Coronary Artery Disease

Robert Roberts1, Chih Chao Chang1

  • 11Cardiovascular Genomics & Genetics, University of Arizona, College of Medicine, Phoenix, AZ, USA; 2Cardiovascular Genomics & Genetics, Phoenix, AZ, USA.

Current Genomics
|October 23, 2020
PubMed

Insights

Genetic Risk Score (GRS) identifies individuals at risk for coronary artery disease (CAD). Lifestyle changes significantly reduce cardiac events, even in those with high genetic predisposition.

Area of Science:

  • Cardiovascular Genetics
  • Preventive Cardiology
  • Genomic Medicine

Background:

  • Coronary artery disease (CAD) is the leading global cause of mortality, necessitating effective primary prevention strategies.
  • Identifying individuals at high risk for CAD is challenging, despite 40-60% of predisposition being genetic.
  • Genome-Wide Association Studies have identified numerous genetic risk variants for CAD, summarized by a Genetic Risk Score (GRS).

Purpose of the Study:

  • To evaluate the efficacy of Genetic Risk Score (GRS) in identifying individuals susceptible to coronary artery disease (CAD).
  • To assess the impact of lifestyle modifications on mitigating genetically predicted CAD risk.
  • To explore the potential of GRS for primary prevention and risk stratification in asymptomatic populations.

Main Methods:

  • Utilized Genome-Wide Association Studies (GWAS) to identify genetic risk variants for CAD.
  • Calculated Genetic Risk Score (GRS) as a cumulative measure of genetic predisposition to CAD.
  • Analyzed prospective studies, including large cohorts like the UK Biobank, to compare GRS with conventional risk factors and assess lifestyle impacts.

Main Results:

  • Genetic Risk Score (GRS) assessment demonstrated superiority over conventional risk factors in stratifying CAD risk in large clinical trials and population studies.
  • Favorable lifestyle choices were associated with significant reductions in cardiac events: 46% for general healthy lifestyle and 50% for programmed exercise.
  • The impact of genetic risk for CAD is substantially mitigated by adopting healthy lifestyle changes and appropriate medical therapies.

Conclusions:

  • Genetic Risk Score (GRS) offers a powerful tool for risk stratification in coronary artery disease (CAD) prevention.
  • Integrating GRS into primary prevention strategies, particularly for young, asymptomatic individuals, represents a paradigm shift.
  • Proactive risk identification and intervention, informed by GRS and lifestyle factors, can significantly reduce the incidence and spread of CAD.
Abstract

Keywords:
Genome-wide association studiescoronary artery diseasegenetic risk stratificationgenetic risk variantsgeneticsgenomicpreventionprimary

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