双重暴露多基因分数相互作用突出显示了社会群体之间的差异,即受益所需的比例
1Center for Integrative Genomics and School of Biological Sciences, Georgia Institute of Technology Atlanta, GA 30302.
medRxiv : the preprint server for health sciences
|August 12, 2024
概括
多基因分数 (PGS) 与环境暴露的相互作用放大了疾病的遗传风险. 有害暴露显著增加疾病风险,突出需要进行包容性全基因组关联研究.
科学领域:
- 基因组学就是基因组学.
- 流行病学 流行病学
- 精准医学是一门精准的医学.
背景情况:
- 多基因分数 (PGS) 对基因组医学至关重要,但它们在不同种群中的可转移性令人担忧.
- 社会群体之间疾病患病率的差异影响了PGS和风险之间的关系.
- 了解PGS-by-Exposure (PGSxE) 相互作用对于公平的临床实施至关重要.
研究的目的:
- 量化七种常见疾病和75种暴露的PGSxE相互作用.
- 评估这些相互作用对预测准确性和疾病风险的影响.
- 引入和评估所需的比例以获益 (PNB) 度量.
主要方法:
- 在英国生物银行 (n=408,801) 的白-英国子集中分析PGSxE相互作用 (n=408,801).
- 评估了7种疾病和75种暴露的24,198个PGSxE模型.
- 引入并计算了获得福利所需的比例 (PNB).
主要成果:
- 测试的PGSxE模型中有3.1%具有统计学意义,超过了机会预期.
- 预测准确度在高风险暴露和相互作用条件下显著提高.
- 诸如不良饮食和社会决定因素等不良暴露会放大遗传效应.
结论:
- PGSxE相互作用是显著的,特别是在不良暴露下放大遗传风险.
- 高风险暴露的个体显示,从干预中获得的潜在益处更大.
- 未来的全基因组关联研究需要更多样化的社会经济抽样.
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