Established polygenic risk score for hypercholesterinemia demonstrates discriminatory value and risk stratification in an independent German Cohort

· 2026-09-04 · 原文

DOI：10.64898/2026.09.01.26361969v1?rss=1

Polygenic risk scores (PRS) have emerged as promising tools for stratifying inherited disease risk, yet their translation into clinical practice is constrained by a critical and frequently unmet requirement: demonstration that scores derived in one cohort retain discriminatory value when applied independently in a different population. For suspected familial hypercholesterolemia (FH), a substantial proportion of patients that meet clinical criteria still test negative for a monogenic cause. These patients are presumed to carry polygenic LDL-C burden, yet PRS validation is still scarce. Here, we evaluated a published hypercholesterolemia PRS (PGS000936) spanning 5,386 genome-wide loci. We tested the score in 117 monogenic-negative hypercholesterolemia cases and 496 controls from the German

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1. 人话版

For suspected familial hypercholesterolemia (FH), a substantial proportion of patients that meet clinical criteria still test negative for a monogenic cause.

2. 领域脉络

These patients are presumed to carry polygenic LDL-C burden, yet PRS validation is still scarce.

3. 机制拆解

摘要未展开方法细节——精读时重点看方法/模型部分。

4. 证据与数字

Here, we evaluated a published hypercholesterolemia PRS (PGS000936) spanning 5,386 genome-wide loci.

We tested the score in 117 monogenic-negative hypercholesterolemia cases and 496 controls from the German

5. 反例与边界

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