Impulse-Control and Conduct Disorders

Genetic Risk for Sleep Problems May Also Predict Cannabis Use Behaviors

Emily Pond
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Cannabis and its synthetic cannabinoids have been studied for medicinal properties across multiple d
Examining the potential shared genetic liability of sleep deficits and cannabis use behaviors using multiple genomic methods.

Study results published in the journal Sleep suggest that certain genes may predispose individuals to both cannabis use and sleep deficits. Using summary statistics from existing genome wide association studies (GWAS), investigators generated polygenic risk scores (PRSs) that were able to predict sleep problems with high accuracy. PRSs for insomnia were also able to predict the age of first cannabis use, as well as lifetime cannabis use, suggesting a common genetic liability between the two phenotypes.

While the relationship between cannabis use and sleep behavior has been extensively studied, the precise effect of cannabinoids on sleep remains unclear. To examine genetic correlations between cannabis behaviors and sleep deficits, investigators used summary statistics from several large cannabis and sleep GWAS. Linkage disequilibrium score (LDSC) regression was used to calculate correlations between cannabis and sleep traits. GWAS summary data were also used to generate PRSs for sleep-related behaviors, including chronotype, sleep duration, and insomnia. The capacity of these PRSs to also predict cannabis measures was tested in participants from existing twin- and family-based community studies in the United States. This target cohort comprised individuals from the Antisocial Drug Dependence cohort in Colorado (n=622) and the Genetics of Antisocial Drug Dependence cohort (n=138) in Colorado and California. The primary outcomes were cannabis use-related measures, including lifetime cannabis use and cannabis use disorder (CUD). Logistic regression was used to assess the predictive ability of sleep deficit PRSs for cannabis behaviors. Models were adjusted for age, sex, and ancestral principal components.  

Using data from the GWAS studies, the LDSC identified significant positive genetic correlations between lifetime cannabis use and the eveningness chronotype (P <.001), a diurnal sleep-wake pattern characterized by alertness in the evening. CUD was significantly associated with both short sleep duration (P =.017) and insomnia (P =.020).

In the target cohort, the insomnia PRS predicted a younger age of first cannabis use (odds ratio [OR], 0.91; 95% CI, 0.84-0.99; P =.023) and increased number of lifetime CUD symptoms (OR, 1.09; 95% CI, 1.02-1.17; P =.019). These associations persisted after additional adjustments for current depression and past 180-day alcohol and tobacco use. The eveningness chronotype PRS significantly predicted lifetime cannabis use (OR, 1.21; 95% CI, 1.01-1.45; P =.042) in initial models, though not after adjustments for depression and other substance use.

This study provides genomic evidence for a relationship between sleep deficits and cannabis use. These data corroborate results from prior twin studies, which suggest that CUD may be partially explained by genetic liability rather than environmental influence alone. However, data generalizability is limited as the target cohort included only patients of European ancestry to reflect the genetic makeup of the GWAS data. Further research in larger, more diverse cohorts is necessary to confirm these findings. “Future studies should consider novel genomic methods to examine potential genes as well as specific genetic causal pathways for these relationships,” the investigators wrote.

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Reference

Winiger EA, Ellingson JM, Morrison CL, et al. Sleep deficits and cannabis use behaviors: an analysis of shared genetics using linkage disequilibrium score regression and polygenic risk prediction [published online September 16, 2020]. Sleep. doi: 10.1093/sleep/zsaa188