title: Genetic variation in FAAH is associated with cannabis use disorders in a young adult sample of Mexican Americans.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Whitney E
authors.initials: WE
authors.lastname: Melroy-Greif
authors.affiliation: Department of Genetics and Neurology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Wilhelmsen
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: cindye@scripps.edu.
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Ehlers
mesh_terms: D000328:Adult; D000483:Alleles; D000581:Amidohydrolases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D002189:Marijuana Abuse / Q000208:ethnology* / Q000235:genetics*; D017058:Mexican Americans / Q000235:genetics* / Q000523:psychology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000099252:Fatty Acid Amide Hydrolases
keywords: Cannabis dependence; Gene-based test; Human genetic association study