Cannabis use and genetic predisposition for schizophrenia: a case-control study

BACKGROUND: Cannabis use may be a risk factor for schizophrenia. Part of this association may be explained by genotype-environment interaction, and part of it by genotype-environment correlation. The latter issue has not been explored. We investigated whether cannabis use is associated with schizophrenia, and whether gene-environment correlation contributes to this association, by examining the prevalence of cannabis use in groups with different levels of genetic predisposition for schizophrenia.

METHOD: Case-control study of first-episode schizophrenia. Cases included all non-Western immigrants who made first contact with a physician for schizophrenia in The Hague, The Netherlands, between October 2000 and July 2005 (n=100; highest genetic predisposition). Two matched control groups were recruited, one among siblings of the cases (n=63; intermediate genetic predisposition) and one among immigrants who made contact with non-psychiatric secondary health-care services (n=100; lowest genetic predisposition). Conditional logistic regression analyses were used to predict schizophrenia as a function of cannabis use, and cannabis use as a function of genetic predisposition for schizophrenia.

RESULTS: Cases had used cannabis significantly more often than their siblings and general hospital controls (59, 21 and 21% respectively). Cannabis use predicted schizophrenia [adjusted odds ratio (OR) cases compared to general hospital controls 7.8, 95% confidence interval (CI) 2.7-22.6; adjusted OR cases compared to siblings 15.9 (95% CI 1.5-167.1)], but genetic predisposition for schizophrenia did not predict cannabis use [adjusted OR intermediate predisposition compared to lowest predisposition 1.2 (95% CI 0.4-3.8)].

CONCLUSIONS: Cannabis use was associated with schizophrenia but there was no evidence for genotype-environment correlation.