Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nat Commun. 2022 Jun 21;13(1):3549. doi: 10.1038/s41467-022-31080-2.
In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS is selected by optimizing the coefficient of variation (CV) across estimated effect sizes from multiple potential PRS using the same GWAS, after which the 3 trait-specific PRSs are combined via an unweighted sum called "PRSsum", forming the HTN-PRS. The HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up. This association is further confirmed in age-stratified analysis. In an independent biobank of 40,201 individuals, the HTN-PRS is confirmed to be predictive of increased risk for coronary artery disease, ischemic stroke, type 2 diabetes, and chronic kidney disease.
在对来自不同队列和生物库的 52436 名 17-90 岁个体进行的多阶段分析中,我们针对高血压风险和进展构建并验证了一种多基因风险评分(PRS)。分别使用全基因组关联研究(GWAS)对收缩压、舒张压和高血压进行 PRS 训练。对于每种特征,通过优化来自同一 GWAS 中多个潜在 PRS 的估计效应大小的变异系数(CV)来选择 PRS,然后通过称为“PRSsum”的无权重和将 3 种特征特异性 PRS 组合在一起,形成 HTN-PRS。HTN-PRS 与随访 4-6 年后的现患和新发高血压均相关。在一个独立的 40201 名个体的生物库中,HTN-PRS 被证实可预测冠状动脉疾病、缺血性中风、2 型糖尿病和慢性肾脏病的风险增加。