甲素水平和心房风险:双向和多变量门德尔随机化分析的见解
Fang Ye1, Ruya Zhou1, Haiying Lin2
1Department of Cardiology, Lishui People's Hospital, Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui, Zhejiang, China.
International journal of genomics
|October 31, 2025
概括
高水平的甲素O与增加心房动 (AF) 风险有遗传联系. 这表明甲素可能在AF发育中发挥作用,提供潜在的新治疗点.
科学领域:
- 心血管遗传学 心血管遗传学
- 蛋白质组学是指蛋白质组学.
- 分子生物学分子生物学
背景情况:
- 心房动 (AF) 是一种普遍的心律失常,对健康有重大影响.
- 全基因组关联研究 (GWAS) 已经确定了AF风险变异,但像甲素这样的蛋白质分解酶的作用尚不清楚.
研究的目的:
- 调查基因决定的甲素水平与心房动风险之间的因果关系.
- 通过使用孟德尔随机化来探索 cathepsins 在心房的发病过程中的作用.
主要方法:
- 在欧洲祖先数据上使用双向和多变量门德尔随机化 (MR).
- 采用了来自INTERVAL研究和AF GWAS元分析数据的9种cathepsin的遗传仪器.
- 进行了逆方差加权 (IVW),MR-Egger和加权中位数分析,具有灵敏度和反向MR分析.
主要成果:
- 基因上升的甲素O水平与增加的AF风险有显著的关联 (IVW:p=0.0025,OR=1.06).
- 对于cathepsin O的这种关联在多变量MR分析中仍然很强大.
- 观察到对cathepsin B的暗示性关联,但没有经过多次测试校正;没有检测到反向因果关系.
结论:
- 提供遗传证据,将高甲素O水平与增加的AF风险联系起来.
- 表明cathepsin O,以及有条件的cathepsin B,可能因果关系地参与AF的发病.
- 突出了蛋白质溶解酶作为AF的潜在治疗点;建议在不同的队列中进一步验证.
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