在英国生物银行中,基因与环境的相互作用背后有不同的解释
Arun Durvasula1,2,3,4,5, Alkes L Price4,5,6
1Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
medRxiv : the preprint server for health sciences
|October 4, 2023
概括
基因与环境的相互作用显著影响复杂的特征和疾病. 这项研究引入了新的方法来识别和区分这些相互作用,揭示了它们对人类健康的重大贡献.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 复杂的特征建筑 复杂的特征建筑
- 基因与环境的相互作用 (GxE)
背景情况:
- 基因与环境 (GxE) 相互作用在疾病和复杂特征发展中的作用被广泛假设,但并未得到充分理解.
- 现有的方法缺乏精度来量化和区分各种类型的GxE相互作用.
研究的目的:
- 开发和应用统计方法来量化和区分三种不同类型的GxE相互作用.
- 使用英国生物银行数据调查GxE和基因对性别相互作用对复杂特征和疾病的贡献.
主要方法:
- 开发了三种统计方法:通过环境 (E) 区间的基因相关性进行特定位置GxE检测,使用多基因风险得分 (PRS) 和PRSxE相互作用术语进行全基因组GxE检测,以及比例放大检测.
- 将这些方法应用于33种英国生物库特征 (25种定量,8种疾病) 和10种环境变量 (生活方式,饮食等). ) 的情况.
- 利用模拟来验证拟议方法的敏感性和特异性.
主要成果:
- 确定了19种特征-E对,具有显著的位置特异性GxE (遗传相关性<1),包括白细胞计数和吸烟.
- 检测到28个具有全基因组PRSxE的特征-E对,在E基因之间具有不同的SNP遗传性,例如BMI和体力活动.
- 发现了15个具有全基因组PRSxE的特征-E对,但具有一致的SNP遗传性,包括腰部和部比和电视观看时间.
- 观察到8种疾病特征的显著GxE效应,以及使用生物性别作为E变量时的额外发现.
结论:
- 开发的框架有效量化和区分不同类型的GxE相互作用.
- 基因-环境和基因-性别相互作用在复杂的特征和疾病的变异性中起着重要作用.
- 这些发现为了解基因与环境在人类健康中的复杂相互作用提供了基础.
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