Schizophrenia polygenic risk is associated with child mental health problems through early childhood adversity: evidence for a gene-environment correlation.
Schizophrenia polygenic risk is associated with child mental health problems through early childhood adversity: evidence for a gene-environment correlation.
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DOI：
10.1007/s00787-021-01727-4
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发表时间：
2022-03
影响因子：
6.4
通讯作者：
Kushner SA
中科院分区：
文献类型：
--
作者：
Bolhuis K;Steenkamp LR;Blanken LME;Neumann A;Jansen PR;Hillegers MHJ;Cecil CAM;Tiemeier H;Kushner SA
先前的研究表明，精神分裂症多基因风险预测了一般人群中的许多心理健康问题。然而，目前还不清楚这些联系是通过何种机制产生的。在这里，我们探讨了精神分裂症多基因风险与儿童期逆境引起的心理健康问题之间可能的基因-环境相关性。本研究嵌入在基于人群的R世代研究中，包括N = 1901名参与者，这些参与者具有精神分裂症多基因风险的基因分型，母亲报告儿童期逆境，以及儿童行为检查表测量心理健康问题。在雅芳父母和儿童纵向研究（ALSPAC; N = 3641）中尝试独立重复。采用Poisson回归和统计中介分析来分析关联性。精神分裂症多基因风险负担越高，儿童期逆境暴露越多（P值阈值< 0.5：R代研究，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）。童年逆境部分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被观察到。总之，精神分裂症的遗传易感性通过童年逆境增加了一般儿科人群中精神健康问题的风险。虽然这一发现可能是基因型和心理健康之间的中介因果关系，但我们认为这些观察结果很可能反映了基因-环境相关性，即逆境是父母传递给子女的遗传风险的标志。这些和最近类似的研究结果提出了重要的概念问题，旨在减少儿童逆境的预防性干预措施。在线版本包含补充材料，可通过10.1007/s 00787 -021-01727-4获得。
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. The online version contains supplementary material available at 10.1007/s00787-021-01727-4.
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影响因子：
7.6
作者：
Jaffee, Sara R.;Bowes, Lucy;Arseneault, Louise
通讯作者：
Arseneault, Louise
DOI：
10.1093/bioinformatics/btu848
发表时间：
2015-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Euesden J;Lewis CM;O'Reilly PF
通讯作者：
O'Reilly PF
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
DOI：
10.1073/pnas.1707178114
发表时间：
2017-10-01
影响因子：
11.1
作者：
Krapohl, E.;Hannigan, L. J.;Plomin, R.
通讯作者：
Plomin, R.
影响因子：
56.9
作者：
Kong, Augustine;Thorleifsson, Gudmar;Stefansson, Kari
通讯作者：
Stefansson, Kari