Genetic variation in FAAH is associated with cannabis use disorders in a young adult sample of Mexican Americans.
Open accessAbstract
Background Cannabis is a commonly used drug and studies have shown that a significant portion of the variation in cannabis use disorders (CUDs) is heritable. Five genes known to play a role in the endocannabinoid system and CUDs were examined in a community sample of young adult Mexican Americans (MAs): CNR1, MGLL, FAAH, DAGLA, and DAGLB.Methods Gene-based tests were run to test for association between each gene and two DSM-5 cannabis phenotypes. Subsequent linear regressions were run in PLINK using an additive model to determine which single nucleotide polymorphisms (SNPs) were driving the association.Results FAAH was significantly associated with DSM-5 cannabis use disorder group count (DSM-5 CUD) using a gene-based test (p=0.0035). This association survived Bonferroni correction for multiple testing at p<0.004. Post hoc analyses suggested this association was driven by two common (minor allele frequency >5%) SNPs in moderate linkage disequilibrium, rs324420 and rs4141964, at p=0.0014 and p=0.0023, respectively. In both cases the minor allele increased risk for DSM-5 CUD.Conclusions Genetic variation in FAAH was associated with DSM-5 CUD in MAs. This association was primarily driven by the missense SNP rs324420. In vitro work has provided evidence that the risk allele generates an enzyme with decreased expression and cellular stability. Although this SNP has been previously associated with substance use in the literature, this is the first association in a young adult MA sample.
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A genetic variation of FAAH is associated with CUD.
“Studies have found that a genetic variation of fatty acid amine hydrolase (FAAH), the enzyme responsible for the degradation of endocannabinoids, is associated with CUD 77, 78.”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [78]
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- Authors
- Melroy-Greif, W. E., Wilhelmsen, K. C., & Ehlers, C. L.
- Affiliations
- Scripps Research Institute (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Ehlers, Cindy L.
- Venue
- Drug and Alcohol Dependence
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 166
- Pages
- 249-253
- ISSN
- 0376-8716 (ISSN-L)
- PMC
- PMC4983484
- OpenAlex
- W2470845599
- Cited by
- 26
- References
- 50
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 1 · 2020: 2 · 2019: 7 · 2018: 1 · 2017: 1
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Drug and Alcohol Dependence (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (P50AA006420, P60AA006420, T32AA013525)
- National Institute on Drug Abuse (R01DA030976)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- fatty acid amide hydrolase, cannabis use disorder, endocannabinoid system, genetic association, Mexican Americans, young adults, single nucleotide polymorphisms, CNR1, monoglyceride lipase, heritability, linkage disequilibrium
- MeSH terms
- Fatty Acid Amide Hydrolases, Adult, Alleles, Amidohydrolases, Marijuana Abuse, Female, Gene Frequency, Humans, Male, Phenotype, Linkage Disequilibrium, Mexican Americans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Young Adult
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