罕见和常见的遗传变异在心房的年龄依赖的贡献
Zhanlin Chen1, Peter F Aziz2, Philip Greenland1,3
1Feinberg School of Medicine, Northwestern University, Chicago, IL (Z.C., P.G., A.S.G., G.W.).
Circulation. Genomic and precision medicine
|September 11, 2025
概括
遗传因素影响心房动 (AF) 风险在不同年龄段不同. 单基因变体与所有年龄段的AF有关,特别是年轻人,而多基因风险在老年人中更相关.
科学领域:
- 心血管遗传学 心血管遗传学
- 基因组学就是基因组学.
- 流行病学 流行病学
背景情况:
- 心房动 (AF) 受遗传变异的影响,具有潜在的年龄相关影响.
- "我们所有人"研究计划为超过10万名成年人提供了大量的全基因组测序和电子健康记录数据集.
研究的目的:
- 调查临床,单基因和多基因因素与不同年龄层的AF的关联.
- 确定遗传信息如何影响AF风险预测和发病年龄.
主要方法:
- 对来自"我们所有人"研究计划的100,574名参与者的横截面分析,分为三个年龄组:<45,45-60岁和>60岁.
- 在145个心脏基因中识别致病性/可能致病性变异,并计算多基因风险得分.
- 多变量分析调整了临床因素,以评估与AF的关联,然后对发病年龄进行时间-事件分析.
主要成果:
- 在所有年龄组中,单基变异与AF相关,在45岁以下的人群中相关性最强 (OR,2.1).
- 多基因风险评分与老年人群 (45-60岁和>60岁) 的AF相关,但在最年轻的群体中没有.
- 临床因素显示出AF的显著预测能力 (C指数,0.84),在添加遗传数据 (C指数,0.86) 后略有改善. 单基变异与更早的AF发作有关.
结论:
- 单基因变异会在一生中导致AF风险,特别是在年轻人中,而多基因风险在老年人中更为突出.
- 遗传数据在临床因素之外的AF风险歧视中提供了有限的改善,但与AF早期发病年龄有关.
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