An 8-SNP LDL Cholesterol Polygenic Score: Associations with Cardiovascular Risk Traits, Familial Hypercholesterolemia...

Area of Science:

• Genetics
• Cardiology
• Public Health

Background:

• Familial hypercholesterolemia (FH) is a primary genetic risk factor for coronary heart disease (CHD).
• Current FH management often overlooks polygenic FH, which is more prevalent than monogenic forms.
• Accurate risk stratification for polygenic FH is crucial for effective CHD prevention.

Purpose of the Study:

• To evaluate the clinical utility of an 8-SNP LDLC polygenic score in a Romanian cohort.
• To assess the association of the polygenic risk score (wPRS) with lipid levels, BMI, and premature CHD (PCHD) risk.
• To determine the score's effectiveness in identifying individuals with clinical FH.

Main Methods:

• Recruitment of 97 healthy controls and 125 PCHD patients in central Romania.
• Calculation of a weighted LDLC polygenic risk score (wPRS) based on 8 single nucleotide polymorphisms (SNPs).
• Statistical analysis of wPRS correlations with lipid profiles (LDL-C, HDL-C), DLCN scores, BMI, and PCHD status.

Main Results:

• The wPRS significantly correlated with LDL-C and DLCN scores, predicting LDL-C concentrations.
• Higher wPRS deciles were associated with increased LDL-C, DLCN scores, and BMI, and decreased HDL-C.
• Individuals in the top wPRS percentile showed a threefold increased likelihood of PCHD; wPRS > 45th percentile identified definite FH with high sensitivity.

Conclusions:

• The LDLC polygenic score is a valuable tool for predicting lipid levels and identifying individuals at higher risk for FH and PCHD.
• This genetic score can enhance risk prediction and patient stratification, particularly for polygenic FH.
• These findings represent the first validation of such a genetic tool in Romania, supporting its potential clinical application.