School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China.
J Youth Adolesc. 2022 Aug;51(8):1597-1610. doi: 10.1007/s10964-022-01610-8. Epub 2022 Apr 26.
Research suggests that genetic variants that regulate the hypothalamic-pituitary-adrenal (HPA) axis function moderate the association between parenting and anxiety symptoms, but these studies have primarily focused on (i) individual genes with very small and unreliable effect and (ii) the role of mothers as opposed to fathers. Using a multilocus genetic profile score approach, the current study is the first to examine the moderation effect of HPA-axis multilocus genetic variants on the associations of both maternal and paternal parenting with adolescent anxiety symptoms. In a sample of Chinese Han adolescents (N = 772; 50.1% girls; M = 16.48 ± 1.40 years, range: 15-20 years), a theory-driven multilocus genetic profile score was computed by counting the numbers of alleles that were previously linked to heightened stress reactivity in six HPA-axis related genes. This HPA-axis related multilocus genetic profile score equivalently interacted with both maternal and paternal parenting in the prediction of adolescent anxiety symptoms. Consistent with cumulative polygenic plasticity hypothesis of differential susceptibility model, adolescents with more versus low alleles linked to heightened stress reactivity not only suffered more from poor maternal or paternal parenting quality, but also benefited more from high maternal or paternal parenting quality. However, none of the individual HPA-axis genes within this multilocus genetic profile score yielded a significant gene-by-environment (G × E) interaction when examined in isolation. The findings survived after internal replication analysis and a novel, valid influence statistic DFBETAS analysis, demonstrating the robustness of the results. The current study highlights the potential value of using a multilocus approach to understand G × E effects underlying anxiety symptoms and emphasizes the role of both mothers and fathers in such gene-parenting interactions, especially in Chinese families.
研究表明，调节下丘脑-垂体-肾上腺（HPA）轴功能的遗传变异调节了父母养育方式与焦虑症状之间的关联，但这些研究主要集中在：（i）个体基因的作用非常小且不可靠，（ii）母亲的作用而不是父亲的作用。本研究采用多基因遗传特征评分方法，首次检验了 HPA 轴多基因变异对母亲和父亲养育方式与青少年焦虑症状关联的调节作用。在一个中国汉族青少年样本中（N=772；50.1%为女孩；M=16.48±1.40 岁，范围为 15-20 岁），通过计算先前与 6 个 HPA 轴相关基因中应激反应增强相关的等位基因数量，计算出一个基于理论的多基因遗传特征评分。该 HPA 轴相关多基因遗传特征评分与母亲和父亲养育方式在预测青少年焦虑症状方面同样存在交互作用。与差异易感性模型的累积多基因可塑性假说一致，与应激反应增强相关的多等位基因数量较多的青少年不仅更容易受到不良的母亲或父亲养育质量的影响，而且更容易从高的母亲或父亲养育质量中受益。然而，当单独检查时，多基因遗传特征评分中的个体 HPA 轴基因均未产生显著的基因-环境（G×E）相互作用。该研究结果在内部复制分析和新颖的有效影响统计量 DFBETAS 分析后仍然存在，表明结果具有稳健性。本研究强调了采用多基因方法理解焦虑症状背后的 G×E 效应的潜在价值，并强调了母亲和父亲在这种基因-养育相互作用中的作用，特别是在中国家庭中。
