BACKGROUND AND HYPOTHESIS Schizophrenia has been robustly associated with multiple genetic and environmental risk factors. Childhood adversity is one of the most widely replicated environmental risk factors for schizophrenia, but it is unclear if schizophrenia genetic risk alleles contribute to this association. STUDY DESIGN In this systematic review and meta-analysis, we assessed the evidence for gene-environment correlation (genes influence likelihood of environmental exposure) between schizophrenia polygenic risk score (PRS) and reported childhood adversity. We also assessed the evidence for a gene-environment interaction (genes influence sensitivity to environmental exposure) in relation to the outcome of schizophrenia and/or psychosis. This study was registered on PROSPERO (CRD42020182812). Following PRISMA guidelines, a search for relevant literature was conducted using Cochrane, MEDLINE, PsycINFO, Web of Science, and Scopus databases until February 2022. All studies that examined the association between schizophrenia PRS and childhood adversity were included. STUDY RESULTS Seventeen of 650 identified studies met the inclusion criteria and were assessed against the Newcastle-Ottawa Scale for quality. The meta-analysis found evidence for gene-environment correlation between schizophrenia PRS and childhood adversity (r = .02; 95% CI = 0.01, 0.03; P = .001), but the effect was small and therefore likely to explain only a small proportion of the association between childhood adversity and psychosis. The 4 studies that investigated a gene-environment interaction between schizophrenia PRS and childhood adversity in increasing risk of psychosis reported inconsistent results. CONCLUSIONS These findings suggest that a gene-environment correlation could explain a small proportion of the relationship between reported childhood adversity and psychosis.

中文翻译：

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精神分裂症的多基因风险和童年逆境的经历：系统评价和荟萃分析。

背景和假设 精神分裂症与多种遗传和环境风险因素密切相关。童年逆境是精神分裂症最广泛复制的环境风险因素之一，但尚不清楚精神分裂症遗传风险等位基因是否有助于这种关联。研究设计 在此系统回顾和荟萃分析中，我们评估了精神分裂症多基因风险评分 (PRS) 与报告的儿童逆境之间的基因-环境相关性（基因影响环境暴露的可能性）的证据。我们还评估了与精神分裂症和/或精神病结果相关的基因-环境相互作用（基因影响对环境暴露的敏感性）的证据。本研究已在 PROSPERO (CRD42020182812) 上注册。遵循 PRISMA 准则，使用 Cochrane、MEDLINE、PsycINFO、Web of Science 和 Scopus 数据库搜索相关文献，直至 2022 年 2 月。所有检查精神分裂症 PRS 与童年逆境之间关联的研究都包括在内。研究结果 650 项确定的研究中有 17 项符合纳入标准，并根据纽卡斯尔-渥太华量表进行了质量评估。荟萃分析发现了精神分裂症 PRS 与童年逆境之间基因-环境相关性的证据（r = .02；95% CI = 0.01、0.03；P = .001），但影响很小，因此可能只能解释一小部分童年逆境与精神病之间关联的比例。调查精神分裂症 PRS 与童年逆境在增加精神病风险方面的基因-环境相互作用的 4 项研究报告了不一致的结果。结论 这些研究结果表明，基因-环境相关性可以解释报告的童年逆境与精神病之间的一小部分关系。