TY - JOUR
T1 - The clinical applicability of polygenic risk scores for LDL-cholesterol: considerations, current evidence and future perspectives
AU - Cupido, Arjen J.
AU - Tromp, Tycho R.
AU - Hovingh, G. Kees
N1 - Publisher Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85102601574&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/MOL.0000000000000741
DO - https://doi.org/10.1097/MOL.0000000000000741
M3 - Article
C2 - 33560669
SN - 0957-9672
VL - 32
SP - 112
EP - 116
JO - Current opinion in lipidology
JF - Current opinion in lipidology
IS - 2
ER -