OBJECTIVES Gene-environment interactions increase the risk of psychosis. The objective of this study was to investigate gene-gene and gene-environment interactions in psychosis, including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR), and cannabinoid receptor type 1 (CB1R), lifetime cannabis use, and childhood trauma. METHODS Twenty-three SNVs of genes encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 community-based controls by Illumina HumanCoreExome-24 BeadChip. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software. RESULTS Single-locus analyses among the 23 SNVs for psychosis and gene-gene interactions were not significant (p > 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p < 0.001). Moreover, gene-environment interactions were significant for an SNV in CNR1 and cannabis use. The best-performing model was the combination of CNR1 rs12720071 and lifetime cannabis use (p < 0.001), suggesting an increased risk of psychosis. CONCLUSION Our study supports the hypothesis of gene-environment interactions for psychosis involving T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.

中文翻译：

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与 CNR1 基因变异相关的终生大麻使用和童年创伤会增加患精神病的风险：STREAM 研究的结果。

目标 基因与环境的相互作用会增加患精神病的风险。本研究的目的是调查精神病中基因-基因和基因-环境的相互作用，包括多巴胺-2受体（D2R）、N-甲基-d-天冬氨酸受体（NMDAR）和大麻素受体的单核苷酸变异（SNV） 1 型 (CB1R)、终生吸食大麻和童年创伤。方法 编码D2R（DRD2：rs1799978、rs7131056、rs6275）、NMDAR（GRIN1：rs4880213、rs11146020；GRIN2A：rs1420040、rs11866328；GRIN2B：rs890、rs2）的基因的23个SNV 098469、rs7298664）和 CB1R（CNR1：rs806380、rs806379 、rs1049353、rs6454674、rs1535255、rs2023239、rs12720071、rs6928499、rs806374、rs7766029、rs806378、rs10485170、rs9450898）在143中进行了基因分型Illumina HumanCoreExome-24 BeadChip 对首发精神病患者 (FEPp) 和 286 名基于社区的对照进行了研究。使用非参数多因子降维软件评估基因-基因和基因-环境关联。结果 23 个 SNV 中精神病和基因间相互作用的单基因座分析并不显着（所有比较 p > 0.05）；然而，这两种环境风险因素均与精神病相关（p < 0.001）。此外，基因-环境相互作用对于 CNR1 和大麻使用中的 SNV 具有重要意义。表现最好的模型是 CNR1 rs12720071 与终生大麻使用的组合 (p < 0.001)，表明精神病风险增加。结论 我们的研究支持精神病的基因-环境相互作用的假设，涉及 CNR1 SNV 的 T 等位基因携带者、儿童创伤和大麻使用。