title: Independent and Interactive Effects of OPRM1 and DAT1 Polymorphisms on Alcohol Consumption and Subjective Responses in Social Drinkers.
abstract: BACKGROUND
  The current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers.
  
  
  METHODS
  Participants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol contents (0.03 to 0.1%). DNA was analyzed for OPRM1 AA versus AG/GG (*G) genotypes, DAT1 10-repeat allele (A10) versus 9 or lesser alleles (A9), and ancestral informative markers.
  
  
  RESULTS
  There were significant epistatic interactions between OPRM1 and DAT1 genotypes. Subjective High Assessment Scale scores after alcohol consumption were highest in *G and A9 carriers, and lowest in *G and A10 carriers. Negative subjective effects were also highest in *G and A9 carriers. Effects were similar in a sensitivity analysis limited to Caucasian subjects. There were independent and epistatic interactions on drinking. The OPRM1 *G allele was independently associated with fewer heavy drinking days. The A9 allele was associated with a greater number of drinking days, which was attenuated in carriers of the *G allele.
  
  
  CONCLUSIONS
  These findings highlight the biological importance of interactions between these 2 genes and interactions between brain opioid and dopamine systems.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Elise M
authors.identifier: http://orcid.org/0000-0002-8234-0919
authors.initials: EM
authors.lastname: Weerts
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland.|Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wand
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland.|Department of Mental Health, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Brion
authors.initials: B
authors.lastname: Maher
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Stephens
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Mary E
authors.identifier: http://orcid.org/0000-0003-2009-4115
authors.initials: ME
authors.lastname: McCaul
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D001944:Breath Tests / Q000379:methods; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; C493214:SLC6A3 protein, human
keywords: A118G; Alcohol; Dopamine Transporter Gene; Intermediate Phenotype; Mu Opioid Receptor Gene; Polymorphism