暴露积累驱动了年龄相关的疾病架构和多基因风险评分
Xilin Jiang1,2,3,4,5, Alkes L Price3,4,6, John Danesh1,2,7,8,9,10
1British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge UK.
medRxiv : the preprint server for health sciences
|September 15, 2025
概括
环境变异随着年龄的增长而积累,使复杂的特征和疾病的遗传能力降低. 这种暴露积累模型,而不是基因年龄相互作用,解释了风险模型中年轻人队伍的预测准确度下降.
科学领域:
- 遗传学 遗传学 是一个
- 流行病学 流行病学
- 生物统计学 生物统计学
背景情况:
- 在常见疾病中,遗传和环境因素之间的相互作用取决于年龄.
- 现有的模型不足以解释遗传和环境影响如何在整个生命周期中发生变化.
研究的目的:
- 在复杂的特征和疾病中区分年龄相关的遗传和环境变异.
- 调查衰老对遗传性和风险预测模型的影响.
主要方法:
- 使用了英国生物库的纵向数据,用于16种定量特征 (N=180K) 和9种复杂疾病.
- 应用统计模型来分离依赖年龄的遗传和环境变异.
- 分析了疾病预测的纵向表型相关性和责任值模型.
主要成果:
- 随着年龄的增长,环境变异的积累导致遗传性降低 (特征平均每十年降低17.8%,疾病平均降低18.1%).
- 暴露积累,而不是基因年龄相互作用,主要是导致遗传能力下降的原因.
- 暴露积累模型解释了多基因风险评分 (PRS) 预测精度随年龄的下降的86%.
结论:
- 暴露累积的年龄依赖责任门模型是一种可概括的疾病模型.
- 遗传和非遗传因素的预测准确度随着年龄的增长而下降.
- 年轻的队伍在训练精确的遗传和非遗传风险预测模型方面更有能力.
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