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在脂蛋白中的祖先多样性 (a) 研究有助于解决证据缺口

Moa P Lee¹, Sofia F Dimos¹, Laura M Raffield²

¹Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

|August 30, 2023

概括

脂蛋白 (Lp) 风险在全球范围内很高,但研究往往忽略了多样化的人口. 这项研究揭示了人群特异性的遗传洞察力,并强调了了解Lp (a) 和心血管疾病风险时需要祖先多样性的必要性.

科学领域:

遗传学是一个遗传学.
心血管疾病心血管疾病
人口健康人口健康

背景情况:

脂蛋白 (Lp) 是一个关键的心血管疾病风险因素,影响全球超过15亿人.
目前对Lp的研究主要集中在欧洲人群中,这可能会限制对其全球影响和遗传结构的理解.

研究的目的:

为了澄清Lp的遗传结构 (a) 在祖先多样化的种群中.
评估Lp (a) 多基因风险评分 (PRS) 对风险预测和因果推断的有用性.
为了确定与Lp (a) 相关的种群特异现象效应.

主要方法:

来自非洲,东亚,欧洲,南亚和西班牙裔/拉丁裔人口 (总共超过40万个人) 的遗传数据的分析.
识别Lp(a) 的全基因组显著基因位点,并构建Lp(a) 多基因风险评分 (PRS).
因果推断分析和PRS对表型关联的外部测试.

主要成果:

确定了14个Lp (a) 的全基因组显著位置,其中几个显示出特定于种群的信号.
Lp(a) PRS的准确性中等至高 (R215% - 50%),并且有望排除低风险个体.
在不同人群中观察到Lp(a) 对糖化血红蛋白的异质因果作用,与冠状动脉样硬化的关联是西班牙裔/拉丁裔的特征.

结论:

优先考虑祖先多样性对于解决Lp (a) 研究中的知识差距至关重要.
了解人群特异性遗传因素对于准确的Lp (a) 风险评估和管理至关重要.
多种数据集是释放Lp(a) 作为心血管风险标志物的全部潜力的关键.

关键词:

生物标志物生物标志物流行病学流行病学遗传关联研究遗传关联研究全基因组关联研究研究.

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