Association between genetic and socioenvironmental risk for schizophrenia during upbringing in a UK longitudinal cohort.
Association between genetic and socioenvironmental risk for schizophrenia during upbringing in a UK longitudinal cohort.
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DOI：
10.1017/s0033291720003347
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发表时间：
2022-06
影响因子：
6.9
通讯作者：
Fisher, H. L.
中科院分区：
文献类型：
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作者：
Newbury, J. B.;Arseneault, L.;Caspi, A.;Moffitt, T. E.;Odgers, C. L.;Belsky, D. W.;Sugden, K.;Williams, B.;Ambler, A. P.;Matthews, T.;Fisher, H. L.
关键词：
社会环境特征，如城市化和邻里剥夺与精神病之间的联系已得到证实。然而，一个经久不衰的问题是，这些联系是否存在因果关系。由于精神疾病遗传风险高的个体向下流动到不利的环境中，可能会发生遗传混淆。我们研究了五个遗传风险指标（精神分裂症和抑郁症的多基因风险评分（PRS）、母亲精神病症状、家族精神病史和基于合子的潜在遗传风险）与成长过程中多个地区、社区和家庭水平风险的相关性。数据来自环境风险（E-Risk）纵向双胞胎研究，这是一项具有全国代表性的队列研究，包括2232名出生于1994-1995年的英国双胞胎，一直随访到18岁（93%的保留率）。社会环境风险包括城市化、空气污染、邻里剥夺、邻里犯罪、邻里无序、社会凝聚力、居民流动性、家庭贫困和累积环境风险量表。参与者在18岁时接受了关于精神病经历的私下采访。在所有指标上较高的遗传风险与成长过程中较高的环境有关。例如，精神分裂症PRS （OR = 1.19, 95% CI = 1.06-1.33）、抑郁症PRS （OR = 1.20, 95% CI = 1.08-1.34）、家族史（OR = 1.25, 95% CI = 1.11-1.40）和潜在遗传风险（OR = 1.21, 95% CI = 1.07-1.38）较高的参与者在18岁时积累了更多的精神分裂症社会环境风险。然而，在对遗传风险进行协变量调整后，社会环境风险与精神病经历之间的关联大多仍然显著。在成长过程中，遗传风险与精神分裂症的社会环境风险相关，但目前，社会环境风险与青少年精神病经历之间的关联似乎存在于基因-环境相关性之外。
Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments. We examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994–1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences. Higher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06–1.33), depression PRS (OR = 1.20, 95% CI = 1.08–1.34), family history (OR = 1.25, 95% CI = 1.11–1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07–1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk. Genetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.