Polygenetic risk for coronary artery disease increases hospitalization burden and mortality

Area of Science:

• Genetics and Genomics
• Cardiovascular Disease Research
• Public Health

Background:

• Coronary artery disease (CAD) is a major global health concern and a significant societal cost.
• Genome-wide association studies (GWAS) have identified common genetic variants linked to CAD.
• A genetic risk score (GRS) aggregates single nucleotide polymorphisms (SNPs) to quantify an individual's genetic predisposition to CAD.

Purpose of the Study:

• To determine if a GRS for CAD can predict future hospitalizations.
• To assess the association between GRS and mortality risk.
• To evaluate the predictive value of GRS independently of established risk factors.

Main Methods:

• Utilized data from 23,594 individuals in the Malmö diet and cancer study, free of CAD at baseline.
• Constructed a GRS using 50 SNPs associated with CAD.
• Employed negative binomial regression for hospitalization analysis and Cox proportional hazards regression for mortality risk assessment over a mean follow-up of 17.8 years.

Main Results:

• Individuals in the highest GRS quintile experienced a 10% higher rate of hospitalization (IRR: 1.10) compared to the lowest quintile.
• Hospitalizations were predominantly for cardiovascular reasons (IRR: 1.31) in the highest GRS group.
• A significantly increased risk of cardiovascular disease (CVD) mortality was observed in the highest GRS quintile (HR: 1.44), with no increased risk for non-CVD mortality.

Conclusions:

• Genetic predisposition for CAD, as indicated by GRS, is a significant predictor of hospitalization burden and mortality, particularly from cardiovascular causes.
• The predictive power of GRS for CAD events is evident even when accounting for traditional risk factors.
• Given that GRS-associated risks are potentially modifiable, these findings may guide strategies to reduce healthcare costs and improve longevity.