亲属关系估计偏差转移到使用方差元件的遗传性估计偏差
Zhuoran Hou1,2, Alejandro Ochoa1,2
1Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27705, USA.
bioRxiv : the preprint server for biology
|June 4, 2025
概括
通常用于遗传性研究的亲属关系估计器可以在结构化群体中产生偏见. 波普金估计器是唯一不偏见的方法,确保准确的遗传遗传估计.
科学领域:
- 人口遗传学 人口遗传学
- 量化遗传学 量化遗传学
- 生物统计学 生物统计学
背景情况:
- 遗传性量化了对特征的遗传贡献,这对疾病研究至关重要.
- 变异组件模型需要亲属关系矩阵 (遗传关系矩阵/GRM) 来估计遗传性.
- 众所周知,标准亲属关系估计器在结构化人群中具有偏见.
研究的目的:
- 描述结构化群体中亲属关系估计引起的遗传性估计偏差.
- 在人口结构下评估不同亲属关系估计器的表现.
- 确定一种在多样化的队列中进行遗传性估计的公正方法.
主要方法:
- 在平均值比率 (ROM) 估计器中获得了遗传性偏差的封闭式表达式.
- 利用模拟研究,使用1000个基因组的基因型进行混合和家族结构的模拟研究.
- 分析了三个现实世界的结构化数据集与表型:圣安东尼奥家庭研究,HCHS/SOL,和瘤综合征队列.
主要成果:
- 标准平均比率 (MOR) 估计器显示出显著的偏差,比ROM更严重,由于低频变量.
- 波普金是一位不受偏见的人口亲属关系估计者,在结构化环境中产生了准确的遗传概率估计.
- 在结构化种群中,仅基因统计的估计表现出上升的遗传性偏差.
- 根据人口结构和变异频率,MOR估计器显示了可变偏差 (向下/向上).
结论:
- 标准亲属关系估计器 (ROM,MOR) 导致结构化人群中偏见的遗传概率估计.
- 波普金估计器克服了与人口结构相关的偏见.
- 在多样化的群体中,准确的遗传性估计需要使用像Popkin.com这样的不偏见的亲属关系估计器.
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