Evaluation of Polygenic Risk Scores for Prediction of Coronary Artery Disease in a Greek Case-Control Study

Area of Science:

• Cardiovascular Genetics
• Polygenic Risk Scores
• Population Genetics

Background:

• Coronary artery disease (CAD) is the leading cause of cardiovascular disease (CVD).
• Polygenic risk scores (PRSs) are crucial for assessing genetic predisposition to diseases.
• Improving the predictive accuracy of PRSs for CAD is an active area of research.

Purpose of the Study:

• To evaluate the performance of existing PRSs for CAD in a Greek population.
• To determine the relative contribution of different PRSs to CAD risk prediction.
• To identify the most effective PRS for CAD risk assessment in this cohort.

Main Methods:

• Nine PRSs from the PGS catalog were tested for CAD risk prediction in 924 Greek individuals (390 cases, 534 controls).
• PRS computations were performed using R and snpStats; statistical analyses utilized IBM SPSS Statistics v21.0.
• PRS effectiveness was quantified using the PRS R² metric from PRSice2.

Main Results:

• PGS000747 demonstrated a substantial increase in predictive value for CAD risk factors, by 21.6% (p < 2.63 × 10⁻²⁵).
• PGS000012 showed a modest increase in CAD risk prediction, by 2.2% (p < 9.58 × 10⁻⁴).
• PGS000747 exhibited superior risk discrimination capabilities compared to other tested PRSs.

Conclusions:

• PGS000747 is a highly effective PRS for predicting CAD risk in the studied Greek population.
• The findings underscore the potential of specific PRSs, like PGS000747, in enhancing personalized CAD risk assessment.
• Further validation in diverse populations is warranted to confirm the broad applicability of these PRSs.