Genotype effects of CHRNA7, CNRI and COMT in schizophrenia: Interactions with tobacco and cannabis use

Background: Genetic variations might modify associations between schizophrenia and cannabis or tobacco use. Aims: To examine whether variants within the cannabinoid receptor (CNRI) and α₇ nicotinic receptor (CHRNA7) genes are associated with schizophrenia, and whether these effects vary according to cannabis or tobacco use. We also examined a putative interaction between cannabis and Val¹⁵⁸Met within the catechol-O-methyltransferase gene (COMT). Method: Genotype effects of CHRNA7 and CNRI were studied in a case-control sample of 750 individuals with schizophrenia and 688 controls, with interactions for these genes studied in small subsamples. A case-only design of 493 of the schizophrenia group was used to examine interactions between cannabis use and COMT. Results: There was no evidence of association between schizophrenia and CNRI (OR=0.97, 9596 CI 0.82-1.13) or CHRNA7 (OR=1,07, 95% CI 0.77-1.49) genotypes, or of interactions between tobacco use and CHRNA7, or cannabis use and CNRI or COMT genotypes. Conclusions: Neither CNRI nor CHRNA7 variation appears to alter the risk of schizophrenia. Furthermore, our results do not support the presence of different effects of cannabis use on schizophrenia according to variation within COMT.