Predictive genetic testing for coronary artery disease

Abstract

Coronary artery disease (CAD) is an inflammatory-metabolic disease in which atherosclerotic plaques cause stenosis of the coronary arteries, leading to acute clinical complications such as myocardial infarction. Since CAD is a multifactorial, polygenic disease with a substantial environmental component, individual risk prediction and stratification is often difficult. Recent technological advances have resulted in substantial progress elucidating the impact of common genetic variation on CAD progression. The discovery of common genetic variants, including the chromosome 9p21.3 locus as the strongest and most highly replicated independent genetic CAD risk factor, has stimulated interest in genetic testing for CAD-associated risk variants. The ultimate goal of genotype-based CAD risk prediction is to improve upon the discrimination and stratification offered by conventional risk factors alone. Genotype-based CAD risk prediction may eventually have clinical utility, but not without intrinsic complexities. Are genotype variables superior predictors of risk compared to a family history of CAD? Is a 10-year risk prediction window ambitious enough for the predictive power of genotype data? This review will outline the current state of genotype-based CAD risk prediction and highlight challenging issues integral to the successful implementation of genetic testing for CAD.

Keywords::

• Algorithm
• cardiovascular diagnostic techniques
• cardiovascular disease
• epidemiology
• forecasting
• genomics
• predisposition testing
• genetic variation
• odds ratios
• risk
• risk assessment
• risk factors

Acknowledgments

The authors would like to thank Reina Hassell, Tisha Joy, Piya Lahiry, Matthew Lanktree, and Jian Wang for their helpful comments and discussions regarding the manuscript.

Disclosures: None.

Declaration of interest

CTJ is supported by an Ontario Graduate Scholarship, a Heart and Stroke Foundation Program Grant, and a CIHR Vascular Research Fellowship. RAH is supported by the Jacob J. Wolfe Distinguished Medical Research Chair, the Edith Schulich Vinet Canada Research Chair in Human Genetics (Tier I), the Martha G. Blackburn Chair in Cardiovascular Research, and operating grants from the Canadian Institutes for Health Research, the Heart and Stroke Foundation of Ontario, and Genome Canada through the Ontario Genomics Institute.