通过转录因子机制对人类特征的表现性贡献
Breeshey Roskams-Hieter1,2, Olivier Labayle3, Kelsey Tetley-Campbell1
1MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom.
medRxiv : the preprint server for health sciences
|November 19, 2025
概括
遗传背景影响DNA变异效应的表观性,是使用有针对性的机器学习来探索的. 研究人员确定了许多影响人类特征的DNA变异相互作用,提供了对转录因子结合和性别偏差遗传风险的见解.
科学领域:
- 遗传学 遗传学 是一个
- 生物信息学是一种生物信息学.
- 基因组学就是基因组学.
背景情况:
- 在复杂的特征中,基因背景对DNA变异效应的调节,即表观作用 (epistasis) 是至关重要的.
- 广泛的表皮性相互作用是假设的,但由于效应大小小和统计复杂性,难以检测.
- 针对生物途径内的变异可以减少全基因组关联研究的负担.
研究的目的:
- 为了确定影响人类特征的DNA变体之间的表观相互作用.
- 研究核激素受体 (NHRs) 在这些相互作用中的作用.
- 为了探索性别特异性对特征的遗传影响.
主要方法:
- 结合目标机器学习与9个NHR的实验验证差异结合变体.
- 在英国生物库 (UKB) 中分析了768个特征.
- 雇佣Hotelling的T^2测试,用于测试相互作用效应的显著性.
主要成果:
- 确定了535个两点和185个三点 (变异-变异-性别) 的NHR相互作用,错误发现率<0.05.
- 几乎三分之一的两点相互作用被复制,涉及与不同跨作用变体共享的DNA结合部位和特征.
- 发现了改变转录因子结合的表皮性机制,提供了分子洞察力.
结论:
- 表观相互作用是可以识别的,并有助于人类复杂的特征.
- NHR相互作用为特征确定提供了可信的分子机制.
- 这些发现提供了对各种人类特征和疾病的性别偏差遗传风险的见解.
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