Translating Genomic Analyses into Improved Management of Coronary Artery Disease

Abstract

Human genetic variation can modulate pathophysiologic processes that alter susceptibility to complex disease. Recent genomic analyses have sought to identify how common genetic variation alters susceptibility to coronary artery disease (CAD). From genome-wide association studies (GWAS), common genetic variants in several novel chromosomal loci have been associated with CAD. GWAS identified the 9p21 locus as the strongest independent genetic CAD risk factor, along with 11 additional loci that harbor common genetic variants associated with increased CAD risk. A thorough understanding of human genetic variation and genomic analyses will be crucial to understand how GWAS-identified loci increase susceptibility to CAD. This article outlines the relevance of genetic variation in the elucidation of novel CAD risk factors and the clinical utility of genetic variants in the management and treatment of CAD.

Keywords:

• 9p21
• coronary artery disease
• genetic risk prediction
• genetic variation
• genome-wide association study
• lifetime risk prediction
• myocardial infarction

Financial & competing interests disclosure

Christopher T Johansen is supported by the Canadian Institutes of Health Research (CIHR) Banting and Best Canada Graduate Scholarship and is a CIHR Fellow in Vascular Research. Matthew B Lanktree is supported by the CIHR MD/PhD Studentship Award and is also a CIHR Fellow in Vascular Research. Robert A Hegele is a Career Investigator of the Heart and Stroke Foundation of Ontario (HSFO) and holds the Edith Schulich Vinet Canada Research Chair (Tier I) in Human Genetics, the Martha G Blackburn Chair in Cardiovascular Research and the Jacob J Wolfe Distinguished Medical Research Chair at the University of Western Ontario. This work was supported by the CIHR (MOP-13430, MOP-79523, CTP-79853), the HSFO (NA-6059, T-6018, PRG-4854), Genome Canada through the Ontario Genomics Institute and the Pfizer Jean Davignon Distinguished Cardiovascular and Metabolic Research Award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

AUC: Area under the curve; CAD: Coronary artery disease; CNRI: Clinical Net Reclassification Improvement; FRS: Framingham Risk Score; NRI: Net Reclassification Improvement; ROC: Receiver–operator characteristic.

Additional information

Funding

Christopher T Johansen is supported by the Canadian Institutes of Health Research (CIHR) Banting and Best Canada Graduate Scholarship and is a CIHR Fellow in Vascular Research. Matthew B Lanktree is supported by the CIHR MD/PhD Studentship Award and is also a CIHR Fellow in Vascular Research. Robert A Hegele is a Career Investigator of the Heart and Stroke Foundation of Ontario (HSFO) and holds the Edith Schulich Vinet Canada Research Chair (Tier I) in Human Genetics, the Martha G Blackburn Chair in Cardiovascular Research and the Jacob J Wolfe Distinguished Medical Research Chair at the University of Western Ontario. This work was supported by the CIHR (MOP-13430, MOP-79523, CTP-79853), the HSFO (NA-6059, T-6018, PRG-4854), Genome Canada through the Ontario Genomics Institute and the Pfizer Jean Davignon Distinguished Cardiovascular and Metabolic Research Award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.