Lifetime cannabis use and childhood trauma associated with CNR1 genetic variants increase the risk of psychosis: findings from the STREAM study


Gene-environment interactions increase the risk of psychosis. Aim: 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.


Twenty-three SNVs of genes related to D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R genes (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. Associations between gene-gene and gene-environment were performed using nonparametric multifactor dimensionality reduction software.


Single locus analysis among the 23 SNVs with 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 SNV in CNR1 and cannabis use. The best performing model was the combination between CNR1 rs12720071 and lifetime cannabis use (p<0.001) suggesting an increased risk of psychosis.


Our study supports the hypothesis of gene-environment interactions for psychosis involving the T allele carriers of CNR1 SNVs, childhood trauma and cannabis use in psychosis.n.


Cannabis use; childhood trauma; first-episode psychosis; single nucleotide variants.

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