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Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis.

Publication ,  Journal Article
Carey, CE; Agrawal, A; Zhang, B; Conley, ED; Degenhardt, L; Heath, AC; Li, D; Lynskey, MT; Martin, NG; Montgomery, GW; Wang, T; Bierut, LJ ...
Published in: Journal of abnormal psychology
November 2015

Despite evidence for heritable variation in cannabis involvement and the discovery of cannabinoid receptors and their endogenous ligands, no consistent patterns have emerged from candidate endocannabinoid (eCB) genetic association studies of cannabis involvement. Given interactions between eCB and stress systems and associations between childhood stress and cannabis involvement, it may be important to consider childhood adversity in the context of eCB-related genetic variation. We employed a system-level gene-based analysis of data from the Comorbidity and Trauma Study (N = 1,558) to examine whether genetic variation in six eCB genes (anabolism: DAGLA, DAGLB, NAPEPLD; catabolism: MGLL, FAAH; binding: CNR1; SNPs N = 65) and childhood sexual abuse (CSA) predict cannabis dependence symptoms. Significant interactions with CSA emerged for MGLL at the gene level (p = .009), and for rs604300 within MGLL (ΔR2 = .007, p < .001), the latter of which survived SNP-level Bonferroni correction and was significant in an additional sample with similar directional effects (N = 859; ΔR2 = .005, p = .026). Furthermore, in a third sample (N = 312), there was evidence that rs604300 genotype interacts with early life adversity to predict threat-related basolateral amygdala habituation, a neural phenotype linked to the eCB system and addiction (ΔR2 = .013, p = .047). Rs604300 may be related to epigenetic modulation of MGLL expression. These results are consistent with rodent models implicating 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid metabolized by the enzyme encoded by MGLL, in the etiology of stress adaptation related to cannabis dependence, but require further replication.

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Published In

Journal of abnormal psychology

DOI

EISSN

1939-1846

ISSN

0021-843X

Publication Date

November 2015

Volume

124

Issue

4

Start / End Page

860 / 877

Related Subject Headings

  • Young Adult
  • Receptor, Cannabinoid, CB1
  • Polymorphism, Single Nucleotide
  • Phospholipase D
  • Monoacylglycerol Lipases
  • Middle Aged
  • Marijuana Abuse
  • Male
  • Lipoprotein Lipase
  • Life Change Events
 

Citation

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Carey, C. E., Agrawal, A., Zhang, B., Conley, E. D., Degenhardt, L., Heath, A. C., … Bogdan, R. (2015). Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis. Journal of Abnormal Psychology, 124(4), 860–877. https://doi.org/10.1037/abn0000079
Carey, Caitlin E., Arpana Agrawal, Bo Zhang, Emily D. Conley, Louisa Degenhardt, Andrew C. Heath, Daofeng Li, et al. “Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis.Journal of Abnormal Psychology 124, no. 4 (November 2015): 860–77. https://doi.org/10.1037/abn0000079.
Carey CE, Agrawal A, Zhang B, Conley ED, Degenhardt L, Heath AC, Li D, Lynskey MT, Martin NG, Montgomery GW, Wang T, Bierut LJ, Hariri AR, Nelson EC, Bogdan R. Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis. Journal of abnormal psychology. 2015 Nov;124(4):860–877.

Published In

Journal of abnormal psychology

DOI

EISSN

1939-1846

ISSN

0021-843X

Publication Date

November 2015

Volume

124

Issue

4

Start / End Page

860 / 877

Related Subject Headings

  • Young Adult
  • Receptor, Cannabinoid, CB1
  • Polymorphism, Single Nucleotide
  • Phospholipase D
  • Monoacylglycerol Lipases
  • Middle Aged
  • Marijuana Abuse
  • Male
  • Lipoprotein Lipase
  • Life Change Events