The clinical applicability of polygenic risk scores for LDL-cholesterol: considerations, current evidence and future perspectives

Abstract

Purpose of review: The current review describes the development, clinical relevance and potential caveats of polygenic risk scores (PRS) for LDL cholesterol (LDL-C).

Recent findings: In recent years, a large number of common variants have been shown to have a small effect on LDL-C levels. The aggregate effect of all of these variants on LDL-C levels can be captured in a PRS and an elevated number of LDL-C increasing common variants is considered to be a cause of high LDL-C levels in patients with familial hypercholesterolemia (FH) without a large effect, rare mutation. PRS do not only serve as a tool in diagnostics, but are also helpful in cardiovascular disease (CVD) risk prediction. Moreover, PRS modulate CVD risk even in patients without a monogenic FH. However, future larger scale PRS directly aimed at CVD risk may serve as more sensitive tools to identify individuals with severely increased CVD risk.

Summary: LDL-C PRS help explain part of hypercholesterolemia in a proportion of dyslipidemic patients that do not have monogenic FH. Nevertheless, the CVD risk conferred by current PRS does not appear to match that of monogenic FH. LDL-C PRS are currently not widely used in clinical care.