Genetic predisposition to schizophrenia associated with increased use of cannabis.
paper
Cited
Public
- Authors
- Power, R A; Verweij, K J H; Zuhair, M; Montgomery, G W; Henders, A K; Heath, A C; Madden, P A F; Medland, S E; Wray, N R; Martin, N G
- Year
- 2014
- Journal
- Molecular psychiatry
- PMID
- 24957864
- DOI
- 10.1038/mp.2014.51
- PMCID
- PMC4382963
Cannabis is the most commonly used illicit drug worldwide. With debate surrounding the legalization and control of use, investigating its health risks has become a pressing area of research. One established association is that between cannabis use and schizophrenia, a debilitating psychiatric disorder affecting ~1% of the population over their lifetime. Although considerable evidence implicates cannabis use as a component cause of schizophrenia, it remains unclear whether this is entirely due to cannabis directly raising risk of psychosis, or whether the same genes that increases psychosis risk may also increase risk of cannabis use. In a sample of 2082 healthy individuals, we show an association between an individual's burden of schizophrenia risk alleles and use of cannabis. This was significant both for comparing those who have ever versus never used cannabis (P=2.6 Γ 10(-4)), and for quantity of use within users (P=3.0 Γ 10(-3)). Although directly predicting only a small amount of the variance in cannabis use, these findings suggest that part of the association between schizophrenia and cannabis is due to a shared genetic aetiology. This form of gene-environment correlation is an important consideration when calculating the impact of environmental risk factors, including cannabis use.
Results of polygenic risk scores for schizophrenia predicting variance explained (R2) in cannabis use as both a binary trait of ever vs. never, and as a quantitative trait of lifetime usewithin only users. Polygenic scores were created using different cut-offs for the inclusion of risk variants for schizophrenia, ranging from p=0.0001 to 1.0.
Mean standardized polygenic risk scores for pairs of twins when neither (n=272), one (n=273), or both twins (n=445) had reported use of cannabis. An ordinal regression reported a significant association (p=0.001).
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