Effect of D2R, NMDAR and CB1R genetic variants associated with cannabis use and childhood trauma in first-episode psychosis in a Brazilian population

Introduction Gene-environment interactions increase psychosis risk (Gayer-Anderson et al . Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657). However, identifying the genetic variants involved and how they interact with environmental factors underlying remains challenging. Objectives To investigate whether there are gene-environment in relationships of childhood trauma, lifetime cannabis use, single nucleotide (SNVs) dopamine D2 receptor (D2R: DRD2 ), N-methyl-d-aspartate (NMDAR: GRIN1 , GRIN2A GRIN2B ) cannabinoid type 1 (CB1R: CNR1 psychosis. Methods In a population-based case-control study nested an incident (STREAM, Brazil) (Del-Ben Br J 2019; 215(6):726-729), part EU-GEI consortium 55(5):645-657), 143 first-episode patients 286 community-based controls both sexes aged between 16 64 years were included over period 3 years. Twenty-three SNVs D2R (rs1799978, rs7131056, rs6275), NMDAR ( : rs4880213, rs11146020; rs1420040, rs11866328; rs890, rs2098469, rs7298664), CB1R genes rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898), genotyped from peripheral blood DNA using custom Illumina HumanCoreExome-24 BeadChip. Environmental adversities evaluated Cannabis Experience Questionnaire (Di Forti al. The Lancet 2009; 6(5):427–436) Childhood Trauma (Grassi-Oliveira Rev Saude Publica 2006; 40(2):249-55). Associations performed nonparametric multifactor dimensionality reduction software (version 3.0.2). Results Single locus analysis showed no association among 23 psychosis; however, was significant for polymorphic loci rs12720071 rs7766029 CNR1. best models two-factor representing by combination use (p<0.001), trauma (p<0.05), suggesting increased Additionally, when considering interaction same model, we found to be associated (p<0.001). Conclusions Our supports hypothesis involving T allele carriers (rs12720071 rs7766029), Disclosure Interest None Declared