Sleep deficits and cannabis use behaviors: an analysis of shared genetics using linkage disequilibrium score regression and polygenic risk prediction

Abstract

Study Objectives Estimate the genetic relationship of cannabis use with sleep deficits and eveningness chronotype. Methods We used linkage disequilibrium score regression (LDSC) to analyze genetic correlations between sleep deficits and cannabis use behaviors. Secondly, we generated sleep deficit polygenic risk scores (PRS) and estimated their ability to predict cannabis use behaviors using linear and logistic regression. Summary statistics came from existing genome wide association studies (GWAS) of European ancestry that were focused on sleep duration, insomnia, chronotype, lifetime cannabis use, and cannabis use disorder (CUD). A target sample for PRS prediction consisted of high-risk participants and participants from twin/family community-based studies (European ancestry; n = 760, male = 64%; mean age = 26.78 years). Target data consisted of self-reported sleep (sleep duration, feeling tired, and taking naps) and cannabis use behaviors (lifetime ever use, number of lifetime uses, past 180-day use, age of first use, and lifetime CUD symptoms). Results Significant genetic correlation between lifetime cannabis use and eveningness chronotype (rG = 0.24, p < 0.001), as well as between CUD and both short sleep duration (<7 h) (rG = 0.23, p = 0.017) and insomnia (rG = 0.20, p = 0.020). Insomnia PRS predicted earlier age of first cannabis use (OR = 0.92, p = 0.036) and increased lifetime CUD symptom count (OR = 1.09, p = 0.012). Conclusion Cannabis use is genetically associated with both sleep deficits and an eveningness chronotype, suggesting that there are genes that predispose individuals to both cannabis use and sleep deficits.

Characterization of the genetic relationship between the domains of sleep and circadian-related behaviors with substance use phenotypes

“…For example, genetic associations between lifetime cannabis use and objectively measured later sleep mid-point and decreased accelerometer derived sleep duration are the first reports of a genetic relationship between cannabis use and objective measures in this domain of research. Later sleep midpoint is an objective proxy for an evening chronotype 26,54,55 , and these results corroborate prior subjective findings regarding a genetic relationship between lifetime cannabis use and selfreport evening chronotype 48 . These findings suggest a shared genetic relationship of lifetime cannabis use with circadian-related measures, implying that people who have more evening or nighttime activity are more likely to have used cannabis due to a shared genetic vulnerability.…”

“…We found significant genetic correlations that align with prior findings, including genetic relationships between subjective sleep measures and substance use behaviors involving cannabis 48 , tobacco 44,45 , alcohol 46 , and opioids 47 . We also found novel relationships between subjective measures of sleep and substance use, such as OUD with subjective long sleep duration.…”

“…Twin studies focused on sleep/circadian-related outcomes and substance use are scarce but a few have found genetic correlations between regular cannabis use and both short sleep duration and insomnia 41,42 as well as genetic correlations between an evening chronotype with alcohol quantity and increased binge drinking 43 . Modern genome-wide association studies (GWASs) studies have found genetic correlations amongst subjective sleep deficits and common substance use behaviors including tobacco behaviors such as smoking initiation, smoking cessation, and cigarettes per day 44,45 , alcohol behaviors via scores on The Alcohol Use Disorders Identification Test (AUDIT) 46 , Opioid Use Disorder 47 , and cannabis behaviors such as lifetime cannabis use and Cannabis Use Disorder 48 . GWASs focused on chronotype/circadian-related activities and substance use are sparse.…”

“…GWASs focused on chronotype/circadian-related activities and substance use are sparse. Genetic correlations have been found between an evening chronotype and lifetime cannabis use 48 , but the relationship between the multitude of available substance use and both chronotype and circadian-related activity measures has yet to be explored. Still, the current limited genetically informed results imply that the genes that could be contributing to sleep deficits and circadian-related factors such as chronotype might contribute to substance use and misuse as well or vice versa.…”

Chronotype and mental health: timing seems to matter, but how, why, and for whom?

“…However, that does not preclude the possibility that there is some trait‐like aspect of chronotype that “travels together” with other processes such as impulsivity or sensation‐seeking. Indeed, emerging research suggests shared genetic variance between chronotype and risk for mental problems or cannabis use 8 . Importantly, the nature of chronotype‐mental health associations may vary substantively based on age, sex, gender identity, and race/ethnicity, as illustrated by a small but growing literature 9 .…”