路径多基因风险评分 (pPRS) 用于基因与环境相互作用的分析
W James Gauderman1, Yubo Fu1, Bryan Queme2
1Division of Biostatistics and Health Data Science, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, United States of America.
PLoS genetics
|August 5, 2025
概括
路径定义的多基因风险评分 (pPRS) 提高了对复杂疾病的基因环境相互作用的检测. 这种方法确定了pPRS和非类固醇抗炎药物 (NSAIDs) 在结直肠癌预防中的显著相互作用.
科学领域:
- 遗传学 是一个遗传学.
- 流行病学 流行病学
- 药物基因组学 药物基因组学
背景情况:
- 多基因风险评分 (PRS) 结合了遗传变异来估计疾病风险.
- PRS与环境因素 (PRS x E) 之间的相互作用可以揭示生物机制,并为有针对性的预防提供信息.
- 标准PRS可能缺乏检测PRS x E相互作用的功率,原因是来自非相互作用变体的稀释.
研究的目的:
- 探索路径定义PRS (pPRS) 对于检测PRS x E相互作用的实用性.
- 研究PRS和非类固醇抗炎药物 (NSAID) 在结直肠癌 (CRC) 中的相互作用.
主要方法:
- 使用基因组路径注释开发和模拟路径定义PRS (pPRS).
- 测试了pPRS x E相互作用,并将功率与标准的PRS x E相互作用进行比较.
- 分析了大量的CRC队列 (N=78,253),检查了NSAID使用和PRS x NSAID相互作用.
主要成果:
- 模拟显示pPRS x E测试产生的功率大大超过整体PRS x E测试.
- 在CRC队列中没有发现有意义的整体PRS x NSAID相互作用 (p=0.41).
- 在TGF-β/GRHR通路中的SNP中确定了显著的pPRS x NSAID相互作用 (p=0.0003).
结论:
- 路径定义的PRS显著改善了基因与环境相互作用的检测.
- 无 NSAID 药物根据TGF-β/GRHR通路的遗传风险显示出对CRC的差异性保护作用.
- 针对特定途径内的基因可能会优化基于NSAID的CRC预防策略.
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