Maternal and paternal effects on offspring internalizing problems: Results from genetic and family-based analyses
Maternal and paternal effects on offspring internalizing problems: Results from genetic and family-based analyses
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DOI：
10.1002/ajmg.b.32784
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发表时间：
2020-05-01
影响因子：
2.8
通讯作者：
Middeldorp, Christel M.
中科院分区：
文献类型：
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作者：
Jami, Eshim S.;Eilertsen, Espen Moen;Middeldorp, Christel M.
目前还不清楚父母对后代内在化问题发展的影响在多大程度上是由间接遗传效应来解释的，这些间接遗传效应反映在父母提供的环境中，除了父母传给孩子的基因。在这项研究中，这些影响进行了调查，使用两种创新的方法在一个大的出生队列。采用母亲效应基因组复杂性状分析（M-GCTA），在3,801个母亲-父亲-子女基因型三人组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，使用包括10，688名儿童在内的系谱数据中估计的遗传相关性来估计加性遗传效应、母体和父亲遗传效应以及使用线性混合效应模型的共享家族效应。除了通过父母和孩子之间的遗传途径传递的影响外，母亲或父亲对8岁时的后代焦虑或抑郁症状没有显着的遗传影响。然而，间接的母亲遗传效应解释了一个小的，但不显着的，在M-GCTA（类似于4%）和系谱（类似于8%）分析的儿童抑郁症状的方差比例。我们的研究结果表明，父母对后代内化问题的影响主要是由于遗传变异，而不是父母基因通过环境的间接影响。
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 (similar to 4%) and pedigree (similar to 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.