Department of Vascular Medicine, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.
Curr Opin Lipidol. 2021 Apr 1;32(2):112-116. doi: 10.1097/MOL.0000000000000741.
The current review describes the development, clinical relevance and potential caveats of polygenic risk scores (PRS) for LDL cholesterol (LDL-C).
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.
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.
本综述描述了用于 LDL 胆固醇（LDL-C）的多基因风险评分（PRS）的发展、临床相关性和潜在注意事项。
近年来，大量常见变异已被证明对 LDL-C 水平有微小影响。所有这些变体对 LDL-C 水平的综合影响可以用 PRS 来捕获，并且被认为是家族性高胆固醇血症（FH）患者 LDL-C 水平升高的原因，而这些患者没有大的影响，罕见的突变。PRS 不仅是诊断的工具，而且有助于心血管疾病（CVD）风险预测。此外，PRS 甚至在没有单基因 FH 的患者中也能调节 CVD 风险。然而，未来更大规模的直接针对 CVD 风险的 PRS 可能成为更敏感的工具，以识别 CVD 风险严重增加的个体。
LDL-C PRS 有助于解释一部分血脂异常患者的高胆固醇血症，这些患者没有单基因 FH。然而，目前的 PRS 所带来的 CVD 风险似乎与单基因 FH 不匹配。LDL-C PRS 目前尚未广泛应用于临床护理。
