Exploring the relationship between polygenic risk for cannabis use, peer cannabis use and the longitudinal course of cannabis involvement

Abstract

Background and aims Few studies have explored how polygenic propensity to cannabis use unfolds across development, and no studies have yet examined this question in the context of environmental contributions such as peer cannabis use. Outlining the factors that contribute to progression from cannabis initiation to problem use over time may ultimately provide insights into mechanisms for targeted interventions. We sought to examine the relationships between polygenic liability for cannabis use, cannabis use trajectories from ages 12-30 years and perceived peer cannabis use at ages 12-17 years. Design Mixed-effect logistic and linear regressions were used to examine associations between polygenic risk scores, cannabis use trajectory membership and perceived peer cannabis use. Setting United States. Participants From the Collaborative Study on the Genetics of Alcoholism (COGA) study, a cohort of 1167 individuals aged 12-26 years at their baseline (i.e. first) interview. Measurements Key measurements included life-time cannabis use (yes/no), frequency of past 12-month cannabis use, maximum life-time frequency of cannabis use, cannabis use disorder (using DSM-5 criteria) and perceived peer cannabis use. Polygenic risk scores (PRS) were created using summary statistics from a large (n = 162 082) genome-wide association study (GWAS) of cannabis use. Findings Three trajectories reflecting no/low (n = 844), moderate (n = 137) and high (n = 186) use were identified. PRS were significantly associated with trajectory membership [P = 0.002-0.006, maximum conditional R 2 = 1.4%, odds ratios (ORs) = 1.40-1.49]. Individuals who reported that most/all of their best friends used cannabis had significantly higher PRS than those who reported that none of their friends were users [OR = 1.35, 95% confidence interval (CI) = 1.04, 1.75, P = 0.023]. Perceived peer use itself explained up to 11.3% of the variance in trajectory class membership (OR = 1.50-4.65). When peer cannabis use and the cannabis use PRS were entered into the model simultaneously, both the PRS and peer use continued to be significantly associated with class membership (P < 0.01). Conclusions Genetic propensity to cannabis use derived from heterogeneous samples appears to correlate with longitudinal increases in cannabis use frequency in young adults.

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

“…Depression symptoms were assessed using the Center for Epidemiological Studies-Depression (CES-D) scale 99 with the caveat of the sleep disturbance question being removed due to its direct overlap with our sleep PRS measure (mean = 27.66, SD = 8.96). All regression models also included the first 10 ancestral principal components (PCs 1-10) generated in PLINK as covariates to account for population stratification as is common in Genetic and PRS analysis 100,101 .…”

Variations of cannabis-related adverse mental health and addiction outcomes across adolescence and adulthood: A scoping review

“…Among the 140 included studies, 135 were in English ( 9 – 13 , 16 , 20 , 24 – 151 ) three in French ( 152 – 154 ), one in Spanish ( 155 ) and one was available both in French and English ( 7 ). There was one meta-analysis ( 88 ), one systematic review ( 7 ), two combined meta-analyses and systematic reviews ( 13 , 20 ), 11 literature reviews ( 33 , 61 , 76 , 86 , 87 , 90 , 95 , 110 , 124 , 136 , 152 ), four randomized controlled trials ( 79 , 100 , 112 , 134 ), 61 cohort studies ( 10 , 16 , 26 , 28 , 29 , 32 , 35 , 36 , 40 – 45 , 47 – 50 , 55 , 60 , 62 , 64 , 68 , 69 , 71 , 74 , 78 , 80 , 83 , 92 , 96 , 98 , 104 , 106 – 109 , 111 , 116 , 118 , 119 , 123 , 125 , 128 , 130 ,…”

The intermediary role of adolescent temperamental and behavioral traits on the prospective associations between polygenic risk and cannabis use among young adults of European Ancestry

“…A recent study by Johnson et al . [43] also failed to support an association between PGS CU and lifetime CU or frequency of CU. In their study, PGS CU was predictive of lifetime history of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5) CUD, but the effect disappeared when examined within a subset of ever‐users.…”