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Genetic Risk Score for CAD and Predispositions to CVD and Non-CVD
Study Questions:
Is there a genetic relationship of cardiovascular diseases (CVDs) and non-CVDs with reported coronary artery disease (CAD) comorbidity?
Methods:
A total of 425,196 UK Biobank participants (aged 40-69 years) were used to determine a genetic risk score (GRS) based on 300 CAD-associated variants (CAD-GRS). This score was associated with 22 traits, including risk factors, diseases secondary to CAD, as well as comorbid and non-CV conditions. Sensitivity analyses were performed in individuals free from CAD or stable angina diagnosis.
Results:
Of the total number of participants, about 5% had CAD. Hypercholesterolemia (odds ratio [OR], 1.27) and hypertension (OR, 1.11) were strongly associated with the CAD-GRS, which indicated that the score contained variants predisposing to these conditions. The CAD-GRS was also significant in patients with CAD who were free of CAD risk factors (OR, 1.37). CAD-GRS was highly associated with CAD prevalence (OR, 1.65 per 1 SD of the CAD-GRS). The study observed significant associations between the CAD-GRS and peripheral arterial disease (OR, 1.28), abdominal aortic aneurysms (OR, 1.28), and stroke (OR, 1.08), which remained significant in sensitivity analyses that suggested shared genetic predisposition. The score was also associated with heart failure (OR, 1.25), atrial fibrillation (OR, 1.08), and premature death (OR, 1.04). These associations were abolished in sensitivity analyses that indicated that they were secondary to prevalent CAD. An inverse association was observed between the score and migraine headaches (OR, 0.94).
Conclusions:
A wide spectrum of CV conditions, including premature death, might develop consecutively or in parallel with CAD for the same genetic roots. In conditions like heart failure, the study found evidence that the CAD-GRS could be used to stratify patients with no or limited genetic overlap with CAD risk. Increased genetic predisposition to CAD was inversely associated with migraine headaches.
Perspective:
While interesting, the utility of genetic risk scores to help determine atherosclerotic CVD risk and potential therapeutic interventions including lifestyle is far from having proven value. However, an example of how a clinical benefit could be readily shown is that in the approximate 500,000-patient UK Biobank, approximately 2,000 would have familial hypercholesterolemia, which was documented clinically in only 50 patients.
Keywords: Angina, Stable, Aortic Aneurysm, Abdominal, Atrial Fibrillation, Coronary Artery Disease, Genetics, Heart Failure, Hypercholesterolemia, Hyperlipoproteinemia Type II, Hypertension, Life Style, Metabolic Syndrome, Migraine Disorders, Peripheral Arterial Disease, Primary Prevention, Risk Factors, Stroke
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