在常见疾病中循环蛋白质的遗传概况表明因果蛋白,并改善风险预测
Qianying Ma1,2, Yimin Cai1, Chunyi He1
1Department of Epidemiology and Biostatistics, School of Public Health; State Key Laboratory of Metabolism and Regulation in Complex Organisms, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
Nature communications
|December 12, 2025
概括
这项研究揭示了遗传变异如何影响疾病中的蛋白质水平. 它识别了与疾病风险相关的遗传因素,并开发了更好的疾病管理的预测模型.
科学领域:
- 基因组学就是基因组学.
- 蛋白质组学是指蛋白质组学.
- 系统生物学 系统生物学
背景情况:
- 了解蛋白质表达的遗传调节对于疾病病理学至关重要.
- 遗传变异可以影响疾病风险和进展.
研究的目的:
- 在各种疾病状态中对蛋白质定量特征位点 (pQTL) 进行大规模的基因组-蛋白质组分析.
- 研究遗传变异对蛋白质表达的疾病特异性调节效应.
- 利用遗传和蛋白质数据开发疾病风险的预测模型.
主要方法:
- 在7626名健康个体和28064名患者中对2901个血蛋白进行全基因组pQTL分析.
- 结合关联发现与孟德尔随机化.
- 开发多基因风险评分和蛋白质风险评分,用于疾病预测.
主要成果:
- 在2224个地区确定了25987个独立的pQTL协会.
- 发现疾病特异性pQTL更有可能是疾病风险变体.
- 确定了110种与21种疾病相关的高可信度因果蛋白,包括心血管疾病的Apolipoprotein (a) 和2型糖尿病的血管酶转化酶.
- 开发了风险预测模型,在区分高风险人群方面表现良好.
结论:
- 疾病状态会影响遗传变异对蛋白质表达的影响.
- 与疾病相关的和与疾病不一致的pQTL协会作为疾病进展的调节者.
- pQTL分析和风险预测模型为疾病机制和个性化医学提供了宝贵的见解.
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