Psychosocial moderation of polygenic risk for cannabis involvement: the role of trauma exposure and frequency of religious service attendance.
- Authors
- Meyers, Jacquelyn L; Salvatore, Jessica E; Aliev, Fazil; Johnson, Emma C; McCutcheon, Vivia V; Su, Jinni; Kuo, Sally I-Chun; Lai, Dongbing; Wetherill, Leah; Wang, Jen C; Chan, Grace; Hesselbrock, Victor; Foroud, Tatiana; Bucholz, Kathleen K; Edenberg, Howard J; Dick, Danielle M; Porjesz, Bernice; Agrawal, Arpana
- Year
- 2019
- Journal
- Translational psychiatry
- PMID
- 31636251
- DOI
- 10.1038/s41398-019-0598-z
- PMCID
- PMC6803671
Cannabis use and disorders (CUD) are influenced by multiple genetic variants of small effect and by the psychosocial environment. However, this information has not been effectively incorporated into studies of gene-environment interaction (GxE). Polygenic risk scores (PRS) that aggregate the effects of genetic variants can aid in identifying the links between genetic risk and psychosocial factors. Using data from the Pasman et al. GWAS of cannabis use (meta-analysis of data from the International Cannabis Consortium and UK Biobank), we constructed PRS in the Collaborative Study on the Genetics of Alcoholism (COGA) participants of European (N: 7591) and African (N: 3359) ancestry. The primary analyses included only individuals of European ancestry, reflecting the ancestral composition of the discovery GWAS from which the PRS was derived. Secondary analyses included the African ancestry sample. Associations of PRS with cannabis use and DSM-5 CUD symptom count (CUDsx) and interactions with trauma exposure and frequency of religious service attendance were examined. Models were adjusted for sex, birth cohort, genotype array, and ancestry. Robustness models were adjusted for cross-term interactions. Higher PRS were associated with a greater likelihood of cannabis use and with CUDsx among participants of European ancestry (p < 0.05 and p < 0.1 thresholds, respectively). PRS only influenced cannabis use among those exposed to trauma (R: 0.011 among the trauma exposed vs. R: 0.002 in unexposed). PRS less consistently influenced cannabis use among those who attend religious services less frequently; PRS × religious service attendance effects were attenuated when cross-term interactions with ancestry and sex were included in the model. Polygenic liability to cannabis use was related to cannabis use and, less robustly, progression to symptoms of CUD. This study provides the first evidence of PRS × trauma for cannabis use and demonstrates that ignoring important aspects of the psychosocial environment may mask genetic influences on polygenic traits.
Main effects of cannabis ever use polygenic risk scores on cannabis use and DSM-5 cannabis use disorder symptom count in COGA participants of European ancestry.Double asterisks (**) denote associations that withstand a multiple test correction
Main effects of PRS (p < 0.01 and p < 0.05 p value thresholds) and PRS effects stratified by trauma exposure (no trauma = not exposed to a traumatic event; trauma = exposed to a traumatic event) and frequency of weekly religious service attendance.Main effects of PRS (p < 0.01 and p < 0.05 p value thresholds) and PRS effects stratified by trauma exposure (no trauma = not exposed to a traumatic event; trauma = exposed to a traumatic event) are displayed in a. Main effects of PRS (p < 0.01 and p < 0.05 p value thresholds) and PRS effects stratified by frequency of weekly religious service attendance are displayed in b. PRS had a greater influence on cannabis ever use and DSM-5 CUD symptom count among those who had been exposed to traumatic events (a) and among those who less frequently attended religious services (b)
| Name | Type |
|---|---|
| 1000 Genomes Project | cohort |
| 23andMe | cohort |
| addiction | phenotype |
| ADH1B | gene |
| adolescent alcohol use | phenotype |
| African American | cohort |
| age | phenotype |
| Agnostic local | phenotype |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| alcohol-related problems | phenotype |
| Alcohol Use | phenotype |
| Alcohol Use Disorder | phenotype |
| alcohol use disorders | phenotype |
| alcohol use initiation | phenotype |
| ALDH2 | gene |
| Ancestral PC1 local | cohort |
| Ancestral PCs local | variant |
| ancestry | phenotype |
| angular gyrus | anatomy |
| any attendance local | phenotype |
| assaultive exposures local | phenotype |
| Atheist local | phenotype |
| ATP2A1 | gene |
| attendance after age 18 years local | phenotype |
| attendance before age 18 years local | phenotype |
| birth cohort | cohort |
| Buddhist local | phenotype |
| Cadm2 | gene |
| cannabis dependence | phenotype |
| Cannabis dependence meta-analysis local | cohort |
| cannabis-dependent cases local | phenotype |
| CannabisEverUse local | phenotype |
| Cannabis ever use PRS local | variant |
| cannabis-exposed controls local | phenotype |
| Cannabis-exposed individuals local | phenotype |
| cannabis initiation | phenotype |
| cannabis initiation polygenic risk score local | phenotype |
| cannabis-related problems | phenotype |
| cannabis use | phenotype |
| cannabis use/abuse local | phenotype |
| cannabis use and problems local | phenotype |
| cannabis use disorder | phenotype |
| cannabis use (ever) local | phenotype |
| Cannabis use PRS | phenotype |
| CannabisUsePRS local | variant |
| Catholic local | phenotype |
| cerebellum | anatomy |
| Christian local | phenotype |
| CHRNA2 | gene |
| CHRNA5 | gene |
| church attendance | phenotype |
| cigarettes | phenotype |
| cingulate cortex | anatomy |
| Cnr1 | gene |
| COGA European ancestry cohort local | cohort |
| COGA participants of European ancestry local | cohort |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| CSMD1 | gene |
| CUD | phenotype |
| CUDsx | phenotype |
| CUD symptoms | phenotype |
| dorsolateral prefrontal cortex | anatomy |
| DSM-5 cannabis use disorder symptom count local | phenotype |
| DSM-5 CUD local | phenotype |
| DSM-5 CUD symptom count local | phenotype |
| DSM-5 disorder criteria local | phenotype |
| DSM-IV cannabis-dependence criterion count local | phenotype |
| Dutch twin study local | cohort |
| EA-derived summary statistics local | cohort |
| EA GWAS cohort local | cohort |
| endocannabinoid system | drug |
| European ancestry | cohort |
| ever cannabis use | phenotype |
| family-based sample | cohort |
| frequency of religious service attendance local | cohort |
| frequency of religious service attendance local | phenotype |
| Frequency of religious service attendance local | phenotype |
| frequency of service attendance local | phenotype |
| Frequency of Service Attendance local | phenotype |
| full sample | cohort |
| Fundamentalist Protestant local | phenotype |
| Genetic ancestry local | cohort |
| Genetic Risk for Substance Use Problems local | phenotype |
| genetic variants | cohort |
| Greek-Orthodox local | phenotype |
| hashish | drug |
| heavy drinking | phenotype |
| high-risk cohort local | cohort |
| International Cannabis Consortium | cohort |
| International Cannabis Consortium meta-analysis local | cohort |
| International Consortium on the Genetics of Heroin Dependence local | cohort |
| iPSYCH | cohort |
| iPSYCH cohort | cohort |
| Jewish local | phenotype |
| JewishAffiliation local | phenotype |
| Jewish Religious Affiliation local | phenotype |
| KCNT2 | gene |
| lifetime cannabis use | phenotype |
| Major mental illness local | phenotype |
| marijuana | phenotype |
| men | cohort |
| Moslem local | phenotype |
| NCAM1 | gene |
| nicotine | drug |
| Non-assaultive local | phenotype |
| non-assaultive exposures local | phenotype |
| Not affiliated local | phenotype |
| other drug use | phenotype |
| Other (religious preference) local | phenotype |
| other substance use and disorders local | phenotype |
| Pasman et al.’s cannabis initiation GWAS local | cohort |
| Pasman et al. study local | cohort |
| Pasman meta-analysis local | cohort |
| PC1 local | variant |
| physical abuse | phenotype |
| polygenic liability to cannabis ever use local | phenotype |
| polygenic liability to cannabis use local | phenotype |
| Polygenic liability to cannabis use local | phenotype |
| polygenic risk for cannabis ever use local | phenotype |
| polygenic risk score | cohort |
| polygenic risk score local | other |
| Polygenic risk score (PRS) local | phenotype |
| PolyGxE local | cohort |
| Post-Traumatic Stress Disorder | phenotype |
| Previous GWAS cohorts local | cohort |
| Principal Components 1-3 local | phenotype |
| Principal Components 1–3 local | drug |
| problem cannabis use | phenotype |
| Protestant local | phenotype |
| ProtestantAffiliation local | phenotype |
| Protestant Religious Affiliation local | phenotype |
| PRSxE local | phenotype |
| Psychiatric Genomics Consortium | cohort |
| Psychosocial environment local | cohort |
| RABEP2 local | gene |
| race/ethnicity | phenotype |
| Religion forbidding alcohol use local | phenotype |
| religiosity | phenotype |
| religious preference local | phenotype |
| religious service attendance local | phenotype |
| Religious service attendance local | phenotype |
| Religious Service Attendance local | phenotype |
| ReligiousServiceAttendance local | phenotype |
| Religious service attendance frequency local | phenotype |
| RP11-206M11 local | gene |
| rs1229984 | variant |
| rs1409568 | variant |
| rs143244591 | variant |
| rs146091982 | variant |
| rs16969968 | variant |
| rs56372821 local | variant |
| rs77378271 | variant |
| Russian-Orthodox local | phenotype |
| SCOC local | gene |
| Self-reported race/ethnicity local | cohort |
| Serbian-Orthodox local | phenotype |
| sex | phenotype |
| Sexually assaultive local | phenotype |
| sexually assaultive exposures local | phenotype |
| SLC35G1 | gene |
| social environment local | phenotype |
| social support | phenotype |
| SSAGA | cohort |
| study cohort | cohort |
| Study of Addiction: Genetics and Environment | cohort |
| Study on the Genetics of Alcoholism local | cohort |
| substance use | phenotype |
| Substance use-related health outcomes local | phenotype |
| trauma | phenotype |
| trauma exposure | phenotype |
| UK Biobank | cohort |
| Virginia adult male twins local | cohort |
| weekly attendance local | phenotype |
| White/Caucasian local | phenotype |
| women | cohort |
| Yale-Penn | cohort |
| Yale-Penn study | cohort |
| ZNF704 local | gene |
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External
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|---|---|---|---|---|
| Cannabis use and psychotic-like experiences: A systematic review of biological vulnerability, potency effects, and clinical trajectories. | Ricci V et al. | — | 2025 | → |
| Disentangling heterogeneity in substance use disorder: Insights from genome-wide polygenic scores. | Vilar-Ribó L et al. | — | 2024 | → |
| Gene-environment interaction between gaming addiction and perceived stress in late adolescents and young adults: A twin study. | Hur YM | — | 2024 | → |
| Ubiquitous bias and false discovery due to model misspecification in analysis of statistical interactions: The role of the outcome's distribution and metric properties. | Domingue BW et al. | — | 2024 | → |
| COVID-19 pandemic stressors are associated with reported increases in frequency of drunkenness among individuals with a history of alcohol use disorder. | Meyers JL et al. | — | 2023 | → |
| Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort. | Segura AG et al. | — | 2023 | → |
| The Collaborative Study on the Genetics of Alcoholism: Overview. | Agrawal A et al. | — | 2023 | → |
| The Genetically Informed Neurobiology of Addiction (GINA) model. | Bogdan R et al. | — | 2023 | → |
| Serotonin disruption at gestation alters expression of genes associated with serotonin synthesis and reuptake at weaning. | Fabio MC et al. | — | 2022 | → |
| The genetic aetiology of cannabis use: from twin models to genome-wide association studies and beyond. | Verweij KJH et al. | — | 2022 | → |
| Cannabis use and cannabis use disorder. | Connor JP et al. | — | 2021 | → |
| The ego dampening influence of religion: evidence from behavioral genetics and psychology. | Sasaki JY et al. | — | 2021 | → |