Short communication: Genetic association between schizophrenia and cannabis use

Abstract

Background and aim Previous studies have shown a relationship between schizophrenia and cannabis use. As both traits are substantially heritable, a shared genetic liability could explain the association. We use two recently developed genomics methods to investigate the genetic overlap between schizophrenia and cannabis use. Methods Firstly, polygenic risk scores for schizophrenia were created based on summary statistics from the largest schizophrenia genome-wide association (GWA) meta-analysis to date. We analysed the association between these schizophrenia polygenic scores and multiple cannabis use phenotypes (lifetime use, regular use, age at initiation, and quantity and frequency of use) in a sample of 6,931 individuals. Secondly, we applied LD-score regression to the GWA summary statistics of schizophrenia and lifetime cannabis use to calculate the genome-wide genetic correlation. Results Polygenic risk scores for schizophrenia were significantly (α<0.05) associated with five of the eight cannabis use phenotypes, including lifetime use, regular use, and quantity of use, with risk scores explaining up to 0.5% of the variance. Associations were not significant for age at initiation of use and two measures of frequency of use analyzed in lifetime users only, potentially because of reduced power due to a smaller sample size. The LD-score regression revealed a significant genetic correlation of rg=0.22 (SE=0.07, p=0.003) between schizophrenia and lifetime cannabis use. Conclusions Common genetic variants underlying schizophrenia and lifetime cannabis use are partly overlapping. Individuals with a stronger genetic predisposition to schizophrenia are more likely to initiate cannabis use, use cannabis more regularly, and consume more cannabis over their lifetime.

Cannabis and psychosis: triangulating the evidence

“…1,2 Despite compelling reasons for adapting evidence-based treatments for adults to include families in LMIC, the topic has received surprisingly little attention in the literature about global mental health services and implementation, with with the exception of a few studies that have involved family in the treatment of patients with psychotic disorders, 3 substance abuse, 4 and dementia. 5,6 A review 7 of community and home-based interventions for people with neuropsychiatric disorders in LMIC showed that fewer than 10% of the interventions involved family members.…”

“…For example, studies using genetic data have found evidence possibly consistent with shared genetic aetiology between risk of psychosis and likelihood to use cannabis. 6 Di Forti and colleagues' study asks participants about their cannabis use prior to their first episode psychosis diagnosis, but it is possible that subclinical symptoms might have existed prior to cannabis initiation, meaning that associations in the opposite direction cannot be ruled out.…”

Assessing causality in associations between cannabis use and schizophrenia risk: a two-sample Mendelian randomization study

“…Power et al (2014) found that a genetic risk score for schizophrenia predicted cannabis use in a sample of 2082 healthy individuals. Verweij et al (in press) used linkage disequilibrium (LD) score regression to investigate this association, and found evidence of a genetic correlation between lifetime cannabis use and risk of schizophrenia. This could be interpreted as shared genetic aetiology, but could also reflect a causal association between schizophrenia and risk of cannabis use (Gage et al 2015).…”

Genetic risk for schizophrenia influences substance use in emerging adulthood: An event-level polygenic prediction model

“…for schizophrenia and problematic substance use (Power et al, 2014;Carey et al, 2016;Kalsi et al, 2016;Reginsson et al, 2017;Verweij et al, 2017).…”

“…For instance, recent studies have found that schizophrenia shares modest but significant genetic correlations with cannabis use (Pasman et al, 2018), alcohol use (Clarke et al, 2017), and risk preferences (Linnér et al, 2018). Similarly, several cross-sectional studies have reported that polygenic scores for schizophrenia predict alcohol, amphetamine, cannabis, cocaine, opioid, and sedative use disorders (Power et al, 2014;Carey et al, 2016;Kalsi et al, 2016;Hartz et al, 2017;Reginsson et al, 2017;Verweij et al, 2017). However, while previous studies have related genetic risk for schizophrenia to diagnosed substance use disorders or lifetime substance use, no study has considered how this genetic risk functions in the context of development.…”