评估使用血压多基因风险评分在种族/种族背景群体的使用
Nuzulul Kurniansyah1, Matthew O Goodman1,2, Alyna T Khan3
1Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
Nature communications
|June 2, 2023
概括
多基因风险评分 (PRSs) 可以预测不同群体的血压. 结合多个全基因组关联研究 (GWAS) 的PRS-CSx方法显示了对缩和腹缩血压的卓越性能.
科学领域:
- 遗传学 是一个遗传学.
- 心血管疾病流行病学
- 生物统计学 生物统计学
背景情况:
- 多基因风险评分 (PRS) 越来越多地用于预测基于遗传变异的疾病风险.
- 评估PRS在不同祖先的表现对于公平的医疗保健至关重要.
- 血压 (BP) 调节是复杂的,受到众多遗传因素的影响.
研究的目的:
- 评估各种多基因风险评分 (PRS) 构造方法对血压 (BP) 现型的性能和局限性.
- 为了比较不同的PRS方法,包括聚合和值 (PRSice2),基于LD的 (LDPred2) 和多PRS方法 (PRS-CSx).
- 评估各种自我报告的种族/族群 (亚裔,黑人,西班牙裔/拉丁裔,白人) 的PRS表现.
主要方法:
- 使用PRSice2,LDPred2和PRS-CSx方法构建和比较PRS.
- 利用包括MGB生物库,TOPMed,英国生物库和我们所有人的大规模数据集进行培训和验证.
- 按种族/种族,性别,肥胖状况和年龄组分类的分层PRS绩效分析.
主要成果:
- PRS-CSx方法是多个全基因组关联研究 (GWAS) 中的PRS的加权和,在所有评估的种族/种族背景中,它显示了对缩血压 (SBP) 和腹缩血压 (DBP) 的最佳预测性能.
- 在我们所有人队列中,PRS表现有所不同,女性的预测能力高于男性,在没有肥胖的人群中,以及在中年人群 (40-60岁) 中.
结论:
- 与基于单个GWAS的方法相比,多PRS方法,特别是PRS-CSx,在不同人群中为BP表型提供了改进的多基因风险预测.
- 对BP的PRS的预测实用性受人口因素的影响,突出了对祖先特定和量身定制的PRS开发的需求.
- 需要进一步的研究,以优化PRS对不同人群和高血压风险分层中的特定临床应用.
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