Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use.
BACKGROUND
Genetic variations might modify associations between schizophrenia and cannabis or tobacco use.


OBJECTIVE
To examine whether variants within the cannabinoid receptor (CNR1) and alpha(7) 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 Val(158)Met within the catechol-O-methyltransferase gene (COMT).


METHODS
Genotype effects of CHRNA7 and CNR1were 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 ofthe schizophrenia group was used to examine interactions between cannabis use and COMT.


RESULTS
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 CNR1or COMT genotypes.


CONCLUSIONS
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.
Zammit
Stanley
S
Department of Psychological Medicine, Cardiff University, Heath Park, Cardiff, UK. zammits@Cardiff.ac.uk
Spurlock
Gillian
G
Williams
Hywel
H
Norton
Nadine
N
Williams
Nigel
N
O'Donovan
Michael C
MC
Owen
Michael J
MJ
D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase; D017831:Diagnosis, Dual (Psychiatry); D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008385:Marijuana Smoking / Q000235:genetics*; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D043882:Receptors, Cannabinoid / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D043882:Receptors, Cannabinoid; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002394:Catechol O-Methyltransferase