Department of Statistics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Department of Statistics, Stanford University, Stanford, CA, United States of America.
PLoS Genet. 2023 Jan 23;19(1):e1010620. doi: 10.1371/journal.pgen.1010620. eCollection 2023 Jan.
Estimation of heritability and genetic covariance is crucial for quantifying and understanding complex trait genetic architecture and is employed in almost all recent genome-wide association studies (GWAS). However, many existing approaches for heritability estimation and almost all methods for estimating genetic correlation ignore the presence of indirect genetic effects, i.e., genotype-phenotype associations confounded by the parental genome and family environment, and may thus lead to incorrect interpretation especially for human sociobehavioral phenotypes. In this work, we introduce a statistical framework to decompose heritability and genetic covariance into multiple components representing direct and indirect effect paths. Applied to five traits in UK Biobank, we found substantial involvement of indirect genetic components in shared genetic architecture across traits. These results demonstrate the effectiveness of our approach and highlight the importance of accounting for indirect effects in variance component analysis of complex traits.
遗传力和遗传协方差的估计对于量化和理解复杂性状的遗传结构至关重要,几乎所有最近的全基因组关联研究(GWAS)都采用了这种方法。然而,许多现有的遗传力估计方法和几乎所有估计遗传相关性的方法都忽略了间接遗传效应的存在,即受父母基因组和家庭环境混淆的基因型-表型关联,因此可能导致错误的解释,特别是对于人类社会行为表型。在这项工作中,我们引入了一个统计框架,将遗传力和遗传协方差分解为多个代表直接和间接效应路径的组件。应用于英国生物库中的五个特征,我们发现间接遗传成分在特征之间的共享遗传结构中具有重要作用。这些结果证明了我们方法的有效性,并强调了在复杂特征的方差成分分析中考虑间接效应的重要性。