对心脏代谢蛋白质组特征的观察和门德尔随机化估计的系统比较
medRxiv : the preprint server for health sciences
|December 17, 2025
概括
蛋白质门德尔随机化 (MR) 研究表明,心脏代谢特征主要受到反向因果关系 (影响蛋白质表型) 的影响. 前进的MR (影响蛋白质的表型) 显示了微弱的同意,表明不同的生物途径,并警告不要将蛋白质水平视为直接原因.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 蛋白质组学是指蛋白质组学.
- 心血管和代谢疾病 心血管和代谢疾病
背景情况:
- 蛋白质门德尔随机化 (MR) 对于确定治疗点至关重要.
- 了解观察和遗传蛋白质特征关联之间的差异是有限的.
- 在这些协会中影响方向协议的因素需要进行系统评估.
研究的目的:
- 系统地评估观察和双向两样 MR 估计之间的重叠和方向一致.
- 为了研究25个心脏代谢特征的7,288个血清蛋白质测量.
- 为了澄清蛋白质组关联中反向因果关系与前向因果关系的影响.
主要方法:
- 使用了5,364个人的队列 (AGES-RS).
- 进行双向的双样本门德尔随机化 (MR) 分析.
- 对 7,288 种蛋白质和 25 种心脏代谢特征的观察关联与 MR 估计进行了比较.
主要成果:
- 观察协会与反向 (蛋白质 → 现型) MR 强烈重叠,显示出高度的方向一致 (中位数为100%).
- 观察协会显示,向前 (表型 → 蛋白质) MR的丰富度和方向一致性较弱 (中位数为55%).
- 编码变体负担预测了前向MR的方向一致性,表明对蛋白质结构的影响.
结论:
- 心脏代谢特征蛋白质特征主要是由反向因果关系形成的.
- 前向和反向的MR方法捕捉到很大程度上是正交的生物路径.
- 在解释循环蛋白质水平作为直接因果暴露时,建议谨慎.
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