Endocannabinoid System Genes Interact with Lifetime Trauma Exposure to Predict Marijuana Dependence: A Systems-Level Gene-Based Analysis
Date of Award
Master of Arts (AM/MA)
The discovery of cannabinoid receptors and their corresponding endogenous ligands has spurred interest in associations between this endocannabinoid (eCB) system and marijuana use. However, no consistent patterns have emerged from candidate eCB genetic association studies of marijuana use and misuse. Given reciprocal interactions between the eCB and stress regulatory systems as well as associations between stress and marijuana use, it may be important to consider trauma exposure in the context of eCB-related genetic variation. We employed a system-level gene-based analysis of data from the Study of Addiction: Genetics and Environment (SAGE) to examine whether genetic variation in 8 eCB genes (anabolism: DAGLA, DAGLB, NAPEPLD, catabolism: MGLL, FAAH, binding: CNR1, CNR2, TRPV1; SNPs n=160) and lifetime exposure to physical, sexual, or non-assaultive trauma predicts cannabis dependence (dependent n=573) among individuals who had tried cannabis (n=2680). Significant gene x trauma interactions emerged for CNR2 (p=0.0031) and MGLL (p=0.0471), one of which, CNR2, remained significant after Bonferroni correction at the gene-level. At the single-SNP level, a SNP x trauma interaction emerged for rs6787155 within MGLL (p=0.00007) which survived SNP-level Bonferroni correction. Neither gene had been previously studied in the context of human cannabis
dependence before. No significant main gene-level or SNP-level effects emerged. These results suggest that links between variation in the eCB system and cannabis dependence may be contingent upon lifetime trauma exposure but require replication.
Chair and Committee
Deanna Barch, Jeffrey Zacks, Arpana Agrawal
Carey, Caitlin E., "Endocannabinoid System Genes Interact with Lifetime Trauma Exposure to Predict Marijuana Dependence: A Systems-Level Gene-Based Analysis" (2015). Arts & Sciences Electronic Theses and Dissertations. 381.
Available for download on Wednesday, May 15, 2115
Permanent URL: https://doi.org/10.7936/K7474815