Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Am J Med Genet B Neuropsychiatr Genet. 2020 Jul;183(5):258-267. doi: 10.1002/ajmg.b.32784. Epub 2020 May 1.
It is unclear to what extent parental influences on the development of internalizing problems in offspring are explained by indirect genetic effects, reflected in the environment provided by the parent, in addition to the genes transmitted from parent to child. In this study, these effects were investigated using two innovative methods in a large birth cohort. Using maternal-effects genome complex trait analysis (M-GCTA), the effects of offspring genotype, maternal or paternal genotypes, and their covariance on offspring internalizing problems were estimated in 3,801 mother-father-child genotyped trios. Next, estimated genetic correlations within pedigree data, including 10,688 children, were used to estimate additive genetic effects, maternal and paternal genetic effects, and a shared family effect using linear mixed effects modeling. There were no significant maternal or paternal genetic effects on offspring anxiety or depressive symptoms at age 8, beyond the effects transmitted via the genetic pathway between parents and children. However, indirect maternal genetic effects explained a small, but nonsignificant, proportion of variance in childhood depressive symptoms in both the M-GCTA (4%) and pedigree (8%) analyses. Our results suggest that parental effects on offspring internalizing problems are predominantly due to transmitted genetic variants, rather than the indirect effect of parental genes via the environment.
目前尚不清楚父母对子女内化问题发展的影响在多大程度上可以用间接遗传效应来解释,除了父母传给子女的基因外,这些效应还反映在父母提供的环境中。在这项研究中,使用两种创新方法在一个大型出生队列中研究了这些效应。利用母体效应全基因组复杂性状分析(M-GCTA),在 3801 个母亲-父亲-孩子基因分型三胞胎中估计了后代基因型、母亲或父亲基因型及其协方差对后代内化问题的影响。接下来,利用包括 10688 名儿童在内的家系数据中的遗传相关估计,使用线性混合效应模型估计加性遗传效应、母性遗传效应、父性遗传效应和共享家庭效应。除了通过父母与子女之间的遗传途径传递的效应外,母亲或父亲的遗传效应对 8 岁儿童的焦虑或抑郁症状没有显著影响。然而,间接的母性遗传效应在 M-GCTA(4%)和家系(8%)分析中均解释了儿童抑郁症状中一小部分但无统计学意义的变异。我们的研究结果表明,父母对子女内化问题的影响主要归因于遗传变异的传递,而不是父母基因通过环境的间接效应。