Department of Child and Adolescent Psychiatry, Amsterdam Public Health Research Institute, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Academic Center for Child and Adolescent Psychiatry, De Bascule, Amsterdam, The Netherlands.
Am J Med Genet B Neuropsychiatr Genet. 2020 Jan;183(1):17-25. doi: 10.1002/ajmg.b.32755. Epub 2019 Aug 24.
The development of problem behavior in children is associated with exposure to environmental factors, including the maternal environment. Both are influenced by genetic factors, which may also be correlated, that is, environmental risk and problem behavior in children might be influenced by partly the same genetic factors. In addition, environmental and genetic factors could interact with each other increasing the risk of problem behavior in children. To date, limited research investigated these mechanisms in a genome-wide approach. Therefore, the goal of this study was to investigate the association between genetic risk for psychiatric and related traits, as indicated by polygenetic risk scores (PRSs), exposure to previously identified maternal risk factors, and problem behavior in a sample of 1,154 children from the Amsterdam Born Children and their Development study at ages 5-6 and 11-12 years old. The PRSs were derived from genome-wide association studies (GWASs) on schizophrenia, major depressive disorder, neuroticism, and wellbeing. Regression analysis showed that the PRSs were associated with exposure to multiple environmental risk factors, suggesting passive gene-environment correlation. In addition, the PRS based on the schizophrenia GWAS was associated with externalizing behavior problems in children at age 5-6. We did not find any association with problem behavior for the other PRSs. Our results indicate that genetic predispositions for psychiatric disorders and wellbeing are associated with early environmental risk factors for children's problem behavior.
儿童问题行为的发展与环境因素有关,包括母体环境。两者都受到遗传因素的影响,这些因素也可能相关,也就是说,儿童的环境风险和问题行为可能部分受到相同的遗传因素的影响。此外,环境和遗传因素可能相互作用,增加儿童出现问题行为的风险。迄今为止,有限的研究以全基因组的方法调查了这些机制。因此,本研究的目的是在一个包括 1154 名来自阿姆斯特丹出生的儿童及其发展研究的样本中,调查遗传风险与精神病学和相关特征(由多基因风险评分 (PRS) 表示)、暴露于先前确定的母体危险因素之间的关联,以及儿童在 5-6 岁和 11-12 岁时的问题行为。PRS 是从精神分裂症、重度抑郁症、神经质和幸福感的全基因组关联研究 (GWAS) 中得出的。回归分析表明,PRS 与多种环境风险因素的暴露有关,这表明存在被动的基因-环境关联。此外,基于精神分裂症 GWAS 的 PRS 与儿童在 5-6 岁时的外化行为问题有关。我们没有发现其他 PRS 与问题行为之间的任何关联。我们的结果表明,精神障碍和幸福感的遗传易感性与儿童问题行为的早期环境风险因素有关。