Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
Eur Child Adolesc Psychiatry. 2022 Mar;31(3):529-539. doi: 10.1007/s00787-021-01727-4. Epub 2021 Feb 26.
Previous studies have shown that schizophrenia polygenic risk predicts a multitude of mental health problems in the general population. Yet it is unclear by which mechanisms these associations arise. Here, we explored a possible gene-environment correlation in the association of schizophrenia polygenic risk with mental health problems via childhood adversity. This study was embedded in the population-based Generation R Study, including N = 1901 participants with genotyping for schizophrenia polygenic risk, maternal reporting of childhood adversity, and Child Behaviour Checklist measurement of mental health problems. Independent replication was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3641). Associations were analysed with Poisson regression and statistical mediation analysis. Higher burden of schizophrenia polygenic risk was associated with greater exposure to childhood adversity (P-value threshold < 0.5: Generation R Study, OR = 1.08, 95%CI 1.02-1.15, P = 0.01; ALSPAC, OR = 1.02, 95%CI 1.01-1.03, P < 0.01). Childhood adversities partly explained the relationship of schizophrenia polygenic risk with emotional, attention, and thought problems (proportion explained, range 5-23%). Direct effects of schizophrenia polygenic risk and adversity on mental health outcomes were also observed. In summary, genetic liability to schizophrenia increased the risk for mental health problems in the general paediatric population through childhood adversity. Although this finding could result from a mediated causal relationship between genotype and mental health, we argue that these observations most likely reflect a gene-environment correlation, i.e. adversities are a marker for the genetic risk that parents transmit to children. These and similar recent findings raise important conceptual questions about preventative interventions aimed at reducing childhood adversities.
先前的研究表明，精神分裂症多基因风险可预测普通人群中多种心理健康问题。然而，这些关联是通过哪些机制产生的尚不清楚。在这里，我们通过儿童逆境来探索精神分裂症多基因风险与心理健康问题之间关联的可能基因-环境相关性。本研究嵌入了基于人群的“生育队列研究”（Generation R Study），包括 N = 1901 名接受精神分裂症多基因风险基因分型、母亲报告儿童期逆境和儿童行为检查表测量心理健康问题的参与者。在“雅芳纵向父母与子女研究”（Avon Longitudinal Study of Parents and Children，ALSPAC；N = 3641）中尝试了独立复制。使用泊松回归和统计中介分析来分析关联。较高的精神分裂症多基因风险负担与儿童期逆境暴露的增加相关（Generation R Study，P 值阈值 < 0.5：OR = 1.08，95%CI 1.02-1.15，P = 0.01；ALSPAC，OR = 1.02，95%CI 1.01-1.03，P < 0.01）。儿童逆境在一定程度上解释了精神分裂症多基因风险与情绪、注意力和思维问题的关系（解释比例，范围 5-23%）。精神分裂症多基因风险和逆境对心理健康结果的直接影响也观察到了。总之，精神分裂症的遗传易感性通过儿童期逆境增加了普通儿科人群心理健康问题的风险。尽管这一发现可能是由于基因型和心理健康之间存在中介因果关系，但我们认为这些观察结果最有可能反映出基因-环境相关性，即逆境是父母传递给孩子的遗传风险的标志物。这些和类似的最近发现提出了关于旨在减少儿童逆境的预防干预措施的重要概念问题。
