Integration of Biomarker Polygenic Risk Score Improves Prediction of Coronary Heart Disease

Area of Science:

• Cardiovascular Genetics
• Biomarker Discovery
• Disease Prediction

Background:

• Established coronary heart disease (CHD) biomarkers include blood pressure, cholesterol, and lipoproteins.
• Polygenic risk scores (PRS) are increasingly used for genetic risk prediction.
• Integrating biomarker information into PRS may enhance CHD prediction accuracy.

Purpose of the Study:

• To develop and evaluate a combined polygenic risk score for CHD that incorporates both genetic predisposition and biomarker information (BioPRS).
• To assess the performance of this novel score (CHDBioPRS) in improving CHD genetic prediction compared to standard CHD PRS.
• To investigate the predictive power of CHDBioPRS across different populations and disease onset times.

Main Methods:

• Development of a biomarker-based polygenic risk score (BioPRS) for CHD.
• Creation of a combined score (CHDBioPRS) integrating BioPRS with a standard CHD PRS.
• Validation of CHDBioPRS using UK Biobank data and testing in the FinnGen cohort.

Main Results:

• The BioPRS demonstrated clear predictive ability for CHD.
• CHDBioPRS significantly improved upon the predictive performance of the standard CHD PRS.
• The largest effect of CHDBioPRS was observed in early-onset CHD cases within the FinnGen cohort, with hazard ratios exceeding 2 per standard deviation.

Conclusions:

• Combining polygenic risk scores for CHD and its associated biomarkers (BioPRS) enhances genetic prediction of the disease.
• CHDBioPRS offers improved risk stratification for coronary heart disease, particularly for individuals with early onset.
• This approach holds promise for refining genetic risk assessment and potentially guiding preventative strategies for CHD.