多omics证据支持PROC作为VTE风险的潜在预测因素:孟德尔的随机化研究
Binbin Wan1, Chenwei Zhang2, Zepeng Yu1
1Division of Planned Immunization, Yiwu Center for Disease Prevention and Control, Yiwu, Zhejiang Province, China.
Medicine
|November 15, 2025
概括
这项研究使用了多omics门德尔随机化来识别与静脉血栓栓塞 (VTE) 相关的基因. 关键的基因PROC,DPY19L1P1和MAFF都与此有关,揭示了潜在的药物标用于VTE预防和治疗.
科学领域:
- 遗传学 是一个遗传学.
- 心血管科学 心血管科学
- 药理学 药理学是指药理学的学科.
背景情况:
- 静脉血栓塞栓症 (VTE) 是一种由各种因素影响的重大心血管疾病.
- 了解VTE潜在的遗传和分子机制对于开发有效的治疗方法至关重要.
研究的目的:
- 为了调查多omics数据 (甲基化,表达,蛋白质水平) 和VTE风险之间的因果关系.
- 确定VTE的潜在药物点和药理学关联.
主要方法:
- 利用了从量化特征位点 (QTL) 跨甲基化 (mQTL),表达 (eQTL) 和蛋白质 (pQTL) 水平的研究中的总结级数据.
- 采用基于总结数据的门德尔随机化 (SMR) 和共定位分析,使用FinnGen和英国生物库数据.
- 进行了全现象关联分析和分子对接,用于药物标识.
主要成果:
- 鉴定了PROC,DPY19L1P1和MAFF作为不同奥米克级别的VTE风险因果相关的基因.
- 发现DPY19L1P1与VTE风险增加有关,MAFF与逆风险有关,PROC与甲基化水平的逆风险有关.
- PROC在蛋白质水平上显示出保护作用,并与12种表型相关;确定了3种药物标.
结论:
- 在甲基化,表达和蛋白质水平上澄清了DPY19L1P1,MAFF,PROC和VTE之间的因果关系.
- 通过全现象分析和分子对接,确认了目标基因的功能关联.
- 突出显示PROC作为VTE的潜在保护因子和治疗点.
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