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Genetic variations might modify associations between schizophrenia and cannabis or tobacco use.
To examine whether variants within the cannabinoid receptor (CNR1) 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).
Genotype effects of CHRNA7 and CNR1 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.
There was no evidence of association between schizophrenia and CNR1 (OR=0.97, 95% 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 CNR1 or COMT genotypes.
Neither CNR1 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.
There is compelling evidence for the existence of susceptibility genes for bipolar disorder. Association studies using functional DNA variations are an important approach for identifying these genes. The enzyme catechol-O-methyltransferase (COMT) plays a key role in the degradation of catecholamine neurotransmitters and is a candidate for involvement in bipolar disorder. Recently a common functional genetic polymorphism that underlies population variation in COM Tactivity has been elucidated and a simple assay developed.
In a collaboration involving seven European centres, we have undertaken an association study of this functional polymorphism in 412 unrelated West European caucasian DSM - III-R bipolar patients and 368 ethnically matched controls.
We found no evidence of allelic or genotypic association.
We can conclude that variation at this functional polymorphism does not make an important contribution to bipolar disorder in the Western European population. Future studies using this powerful experimental approach can be expected to contribute to identification of bipolar susceptibility genes.
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