剖析血分子特征的遗传和环境决定因素及其与2型糖尿病风险的联系
Magdalena Sevilla-González1,2,3, Ningyuan Wang4, Paul A Hanson1,3
1Clinical and Translational Epidemiology Unit. Mongan Institute. Massachusetts General Hospital. Boston, MA, 02114, USA.
medRxiv : the preprint server for health sciences
|December 8, 2025
概括
这项研究揭示了遗传和环境因素如何通过血代谢物和蛋白质影响2型糖尿病 (T2D) 风险. 研究结果确定了导致T2D差异的关键分子通路,从而推进了预防的精准医学.
科学领域:
- 基因组学和蛋白质组学
- 代谢学 代谢学 代谢学
- 流行病学 流行病学
- 精准医学是一门精准的医学.
背景情况:
- 2型糖尿病 (T2D) 在人口中呈现出显著的发病率差异,由复杂的遗传,环境,文化和社会经济因素驱动.
- 导致这些T2D差异的潜在分子机制在很大程度上仍未被探索.
- 血代谢物和蛋白质作为对T2D风险的遗传和环境影响的关键整合剂,提供了对疾病发病的洞察力.
研究的目的:
- 量化可归因于环境和遗传祖先领域的血蛋白质和代谢特征的变异.
- 通过因果推理识别环境和遗传祖先影响的分子途径,这些途径有助于T2D风险.
- 阐明分子媒介在T2D的种族/民族差异中的作用.
主要方法:
- 分析了来自3,360名MESA和1,333名妇女健康倡议参与者的血蛋白质组和代谢组数据.
- 变异分解分为生物,遗传祖先,生活方式和社会决定性领域.
- 应用双样本门德尔随机化来区分环境和遗传对T2D风险的贡献.
主要成果:
- 生物学和生活方式因素解释了分子形状的最大差异;遗传血统和社会决定因素有非冗余的贡献.
- 与脂质/脂蛋白变异相关的遗传祖先;与免疫/炎症特征相关的种族/种族和社会经济因素.
- 环境影响的代谢物和血管炎症蛋白与较高的T2D风险相关; 门德尔随机化证实了七种脂质和IGFBP3的因果作用.
结论:
- 确定了分子概况变化的遗传和非遗传来源,揭示了导致T2D风险的途径.
- 突出了T2D差异的可修改分子媒介,为预防策略提供了潜在的因果目标.
- 通过发现减轻T2D风险和健康不平等的关键分子标,先进的精确医学.
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