Polygenic contribution for familial hypercholesterolemia (FH).

Area of Science:

• Genetics
• Cardiology
• Pharmacogenomics

Background:

• Familial hypercholesterolemia (FH) is a genetic disorder causing high LDL-C.
• Identifying the genetic basis (monogenic vs. polygenic) is crucial for FH management.
• Mutation-negative FH individuals often have complex genetic underpinnings.

Purpose of the Study:

• To review polygenic risk scores (PRS) applied to FH cohorts.
• To assess the role of PRS in diagnosing hypercholesterolemia in FH.
• To explore PRS utility in risk stratification and personalized therapy for FH.

Main Methods:

• Review of studies utilizing PRS in FH cohorts.
• Analysis of single-nucleotide polymorphisms (SNPs) associated with LDL-C and Lp(a).
• Evaluation of PRS in identifying polygenic hypercholesterolemia in mutation-negative FH.

Main Results:

• PRS are effective in identifying polygenic hypercholesterolemia in FH mutation-negative individuals.
• Elevated LDL-C PRS correlate with increased atherosclerotic cardiovascular disease risk in FH.
• Polygenic basis may influence lipid-lowering therapy response and Lp(a) levels in FH.

Conclusions:

• PRS are valuable tools for FH diagnosis and should be integrated into diagnostic strategies.
• Further development of specific LDL-C PRS is warranted.
• PRS aid in refining cardiovascular risk prediction and personalizing FH treatment.