title: Alcohol consumption mediates the relationship between ADH1B and DSM-IV alcohol use disorder and criteria.
abstract: OBJECTIVE
  A single nucleotide variation in the alcohol dehydrogenase 1B (ADH1B) gene, rs1229984, produces an ADH1B enzyme with faster acetaldehyde production. This protective variant is associated with lower alcohol consumption and lower risk for alcohol use disorders (AUDs). Based on the premise that faster ADH1B kinetics decreases alcohol consumption, we formally tested if the association between ADH1B variant rs1229984 and AUDs occurs through consumption. We also tested whether the association between rs1229984 and each of the 11 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), AUD criteria occurs through consumption.
  
  
  METHODS
  A total of 1,130 lifetime drinkers from an Israeli household sample were assessed with a structured interview and genotyped for rs1229984 (protective allele frequency = 0.28). Logistic regression evaluated the association between rs1229984 and each phenotype (AUDs, 11 individual DSM-IV criteria). For phenotypes significantly related to rs1229984, the effect through consumption was tested with logistic regression and bootstrapping.
  
  
  RESULTS
  ADH1B rs1229984 was significantly associated with AUDs and six criteria, with odds ratios ranging from 1.32 to 1.96. The effect through consumption was significant for these relationships, explaining 23%-74% of the total ADH1B effect.
  
  
  CONCLUSIONS
  This is the first study to show that ADH1B rs1229984 is related to 6 of the 11 DSM-IV AUD criteria and that alcohol consumption explained a significant proportion of these associations and the association of ADH1B with AUDs. Better understanding of the relationship between ADH1B and the DSM-IV AUD criteria, including effects through consumption, will enhance our understanding of the etiologic model through which AUDs can occur.
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Bari
authors.initials: B
authors.lastname: Kilcoyne
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, New York State Psychiatric Institute, New York, New York.
authors.forename: Dvora
authors.initials: D
authors.lastname: Shmulewitz
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Jacquelyn L
authors.initials: JL
authors.lastname: Meyers
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, New York State Psychiatric Institute, New York, New York.
authors.forename: Efrat
authors.initials: E
authors.lastname: Aharonovich
authors.affiliation: New York State Psychiatric Institute, New York, New York.
authors.forename: Eliana
authors.initials: E
authors.lastname: Greenstein
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Felsenstein Medical Research Center, Petach Tikva, Israel.
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Felsenstein Medical Research Center, Petach Tikva, Israel, Research Unit, Geha Mental Health Center, Petach Tikva, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Baruch
authors.initials: B
authors.lastname: Spivak
authors.affiliation: Departments of Biochemistry and Molecular Biology, Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.affiliation: Departments of Psychiatry, Genetics and Neurobiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, New York State Psychiatric Institute, New York, New York.
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Hasin
mesh_terms: D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000453:epidemiology* / Q000235:genetics; D019973:Alcohol-Related Disorders / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007557:Israel / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase