对血生物标志物的评估,以确定与周围动脉疾病的因果关联
Pranav Sharma1, Derek Klarin2,3, Benjamin F Voight4,5,6
1Department of Surgery, Perelman School of Medicine (P.S., S.M.D.), University of Pennsylvania, Philadelphia.
Arteriosclerosis, thrombosis, and vascular biology
|March 28, 2024
概括
遗传分析显示,在观察性研究中发现的外周动脉疾病 (PAD) 生物标志物中,只有很小一部分显示出因果关系. 这凸显了需要强有力的证据超越观察数据,以了解PAD的原因.
科学领域:
- 心血管研究研究心血管研究
- 遗传学 是一个遗传学.
- 生物标志物发现发现
背景情况:
- 周围动脉疾病 (PAD) 有许多报告的生物标志物,但由于潜在的混,观察性研究限制了因果推断.
- 评估这些生物标志物的因果影响对于理解PAD病理生理学至关重要.
研究的目的:
- 通过使用遗传因果推断方法,评估假定PAD生物标志物的潜在因果影响.
- 通过遗传证据验证在人类观察研究中发现的生物标志物.
主要方法:
- 从文献中确定了204种循环PAD生物标志物.
- 从全基因组关联研究 (GWAS) 中生成的遗传仪器.
- 在大型队列中使用双样本的门德尔随机化来测试与PAD的生物标志物关联 (退伍军人事务百万退伍军人计划和FinnGen).
主要成果:
- 173个生物标志物被基因仪器仪表.
- 在173个生物标志物中的10个 (5.8%) 在多次测试校正后显示出与PAD的显著关联.
- 相关生物标志物与脂蛋白调节,脂质平衡和蛋白质脂质复合体重塑有关.
结论:
- 遗传因果推断为PAD生物标志物的有效性提供了比单独的观察研究更有力的证据.
- 之前识别的PAD生物标志物的很大一部分缺乏强大的遗传支持.
- 需要进一步的研究来确认PAD与一般动脉样硬化所识别的生物标志物的特异性.
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