Department of Life Sciences, Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London, United Kingdom.
Department of Medicine, Imperial College London, London, United Kingdom.
Mol Genet Genomic Med. 2020 Jun;8(6):e1248. doi: 10.1002/mgg3.1248. Epub 2020 Apr 19.
Severe hypercholesterolemia (HC, LDL-C > 4.9 mmol/L) affects over 30 million people worldwide. In this study, we validated a new polygenic risk score (PRS) for LDL-C.
Summary statistics from the Global Lipid Genome Consortium and genotype data from two large populations were used.
A 36-SNP PRS was generated using data for 2,197 white Americans. In a replication cohort of 4,787 Finns, the PRS was strongly associated with the LDL-C trait and explained 8% of its variability (p = 10 ). After risk categorization, the risk of having HC was higher in the high- versus low-risk group (RR = 4.17, p < 1 × 10 ). Compared to a 12-SNP LDL-C raising score (currently used in the United Kingdom), the PRS explained more LDL-C variability (8% vs. 6%). Among Finns with severe HC, 53% (66/124) versus 44% (55/124) were classified as high risk by the PRS and LDL-C raising score, respectively. Moreover, 54% of individuals with severe HC defined as low risk by the LDL-C raising score were reclassified to intermediate or high risk by the new PRS.
The new PRS has a better predictive role in identifying HC of polygenic origin compared to the currently available method and can better stratify patients into diagnostic and therapeutic algorithms.
严重高胆固醇血症（HC，LDL-C＞4.9mmol/L）影响着全球超过 3000 万人。本研究旨在验证一种新的 LDL-C 多基因风险评分（PRS）。
使用全球血脂基因组联盟的汇总统计数据和两个大型人群的基因型数据。
使用 2197 名美国白人的数据生成了一个 36-SNP PRS。在 4787 名芬兰人的复制队列中，PRS 与 LDL-C 特征密切相关，解释了其变异性的 8%（p=10）。在风险分类后，高危组与低危组相比，HC 的风险更高（RR=4.17，p＜1×10）。与目前在英国使用的 12-SNP 升高 LDL-C 评分相比，PRS 解释了更多的 LDL-C 变异性（8%比 6%）。在严重 HC 的芬兰人中，PRS 分别将 66/124（53%）和 55/124（44%）归类为高危，而 LDL-C 升高评分分别将 66/124（53%）和 55/124（44%）归类为高危。此外，用 LDL-C 升高评分定义为低危的严重 HC 个体中，有 54%被重新分类为中危或高危。
与目前可用的方法相比，新的 PRS 在识别多基因起源的 HC 方面具有更好的预测作用，并且可以更好地将患者分层为诊断和治疗算法。
