FEMA-Long:在大型纵向数据集中建模非结构化协差,以发现时间依赖的效应
Pravesh Parekh1, Nadine Parker1, Diliana Pecheva2
1Centre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway.
bioRxiv : the preprint server for biology
|June 4, 2025
概括
通过建模复杂的共变性结构和实现全基因组关联研究 (GWAS),FEMA-Long增强了纵向数据分析. 这种方法揭示了婴儿生长中的时间依赖的遗传效应,为发育生物学提供了新的见解.
科学领域:
- 遗传学和生物信息学
- 统计建模 统计建模
- 发展生物学 发展生物学
背景情况:
- 线性混合效应 (LME) 模型是纵向数据的标准,但通常使用简化的协差结构.
- 高维的纵向数据需要更灵活的协差建模.
- 发现时间依赖的遗传效应需要先进的分析工具.
研究的目的:
- 引入FEMA-Long,这是快速有效的混合效应算法 (FEMA) 的扩展,用于灵活的纵向协差建模.
- 为了使全基因组关联研究 (GWAS) 与时间依赖的遗传效应发现.
- 使用非线性SNP-by-time相互作用分析婴儿生长轨迹 (长度,体重,BMI).
主要方法:
- 开发了FEMA-Long以使用splines建模非结构化协变性和非线性固定效应.
- 整合了线相互作用,以发现时间依赖的固定效应.
- 对68273名婴儿进行了纵向GWAS,在生命的第一年进行了多达6次测量.
主要成果:
- FEMA-Long成功建模了随机效应的动态模式,包括时间变化的遗传性和相关性.
- 确定了几种基因变异,对婴儿生长有时间依赖的影响.
- 证明了发现时间依赖于复杂特征的遗传影响的能力.
结论:
- FEMA-Long为高维纵向数据分析提供了一种计算可处理的方法.
- 该方法有助于在发育研究中发现新的,依赖时间的遗传效应.
- 强调在遗传关联研究中考虑时间动态的重要性.
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