Variants of genes that predispose people to developing schizophrenia also predispose them to using cannabis, a study of more than 2000 people has found.
The discovery suggests that the well-established association between schizophrenia and cannabis use is due, at least in part, to a shared genetic aetiology.
“Our findings here highlight the possibility that this association might be bidirectional in causation, and that the risks of cannabis use could be overestimated”, say Robert Power (Institute of Psychiatry, King’s College London, UK) and fellow researchers writing in Molecular Psychiatry.
People who use cannabis have around a twofold increased risk of psychotic illness, but the nature and direction of causality is unclear. To investigate, Power’s team studied 2082 healthy individuals, of whom 1011 (48.6%) had ever used cannabis. The mean number of lifetime uses was 62.7 and the mean age at first use was 20 years.
Based on genotyping for risk alleles implicated in schizophrenia, each participant was assigned a polygenic risk score that reflected their cumulative burden of schizophrenia risk.
Significantly, these polygenic risk scores were positively associated with ever versus never use of cannabis, as well as with the quantity of cannabis use.
In a separate analysis involving 990 twin pairs (608 dizygotic and 382 monozygotic), the polygenic risk score for schizophrenia was again significantly associated with cannabis use or non-use. Scores were highest for pairs in which both twins reported cannabis use, intermediate for pairs in which only one twin reported use and lowest for those in which neither reported use.
The researchers say their results show that, to some extent, the association between cannabis and schizophrenia is due to a shared genetic aetiology across common variants.
“This is not to say that there is no causal relationship between use of cannabis and risk of schizophrenia, but it does establish that at least part of the association may be due to causal relationship in the opposite direction”, they write.
Power et al note that their findings have important implications for the ongoing debate about the legalisation of cannabis and the potential economic and health impact of the drug.
They add: “These results highlight the blurring between behavioural phenotypes and environment, and have wider implications for how we perceive supposedly environmental risks for disease.”
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