Abstract
BackgroundSchizophrenia is associated with a higher prevalence of cannabis use and cigarette use. However, it is unknown to what extent these associations are due to a shared genetic aetiology. We therefore aim to examine how schizophrenia genetic risk associates with patterns of cigarette and cannabis use in adolescence.MethodsWe analysed repeated measures of cigarette and cannabis use during adolescence in a sample of 5,300 individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort who had at least 3 measures of cigarette and cannabis use between ages 14–19 years. Cigarette and cannabis use data were summarised using longitudinal latent class analysis to identify longitudinal classes of substance use, and associations between polygenic scores for schizophrenia and resulting classes were assessed.ResultsThe schizophrenia polygenic score based on single nucleotide polymorphisms (SNPs) meeting a discovery sample threshold of p ≤ 0.05 was associated with late onset cannabis use as compared to non-use (OR = 1.20; 95% CI = 1.05, 1.37) but not with early onset or cigarette only use latent classes. This association persisted after excluding the CHRNA5-CHRNA3-CHRNB4 nicotinic receptor gene cluster (OR = 1.25; 95% CI = 1.08, 1.44), a locus which has previously been found to strongly associate with schizophrenia.DiscussionThis study found that genetic risk of schizophrenia (as captured by polygenic scores) is associated with late-onset cannabis use but not with other smoking phenotypes in adolescence in ALSPAC. Possible explanations for these results are that schizophrenia and cannabis use have a shared genetic aetiology or that biological risk of schizophrenia leads to cannabis use through secondary mechanisms. These secondary mechanisms may include stress of childhood behavioural problems occurring as a result of biological processes underling schizophrenia. Future analyses involving mediation models may shed some light on factors influencing patterns of substance use in individuals with a high genetic liability for schizophrenia.
Highlights
Maternal depression during pregnancy increased the risk for mood disorders in the offspring slightly but not for schizophrenia nor substance use disorder when compared with the children of mothers without antenatal depression
Schizophrenia is associated with a higher prevalence of cannabis use and cigarette use
The schizophrenia polygenic score based on single nucleotide polymorphisms (SNPs) meeting a discovery sample threshold of p ≤ 0.05 was associated with late onset cannabis use as compared to non-use (OR = 1.20; 95% CI = 1.05, 1.37) but not with early onset or cigarette only use latent classes
Summary
It was used for identifying severe mental disorders in the parents till 1984, when the offspring were of age. Maternal depression during pregnancy combined with parental severe mental disorder increased the risks for severe mental disorders in the offspring widely. In the offspring of antenatally depressed mother and a father with severe mental disorder the risk was elevated only for schizophrenia (7.5; 2.2–26.2). Discussion: Maternal depression during pregnancy increased the risk for mood disorders in the offspring slightly but not for schizophrenia nor substance use disorder when compared with the children of mothers without antenatal depression. Maternal antenatal depression combined with parental severe mental disorder increased the risks for all of these severe mental disorders in the adult offspring. The risk was highest for schizophrenia in the offspring of antenatally depressed mother and a father with severe mental disorder. Stanley Zammit*,1, Hannah Jones, Suzanne Gage, Jon Heron, George Davey Smith, Glyn Lewis, Michael O’Donovan, Michael Owen, James Walters, Marcus Munafò2 1Cardiff University; 2University of Bristol; 3University of Liverpool; 4University College London
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