title: An ADH1B variant and peer drinking in progression to adolescent drinking milestones: evidence of a gene-by-environment interaction.
abstract: BACKGROUND
  Adolescent drinking is an important public health concern, one that is influenced by both genetic and environmental factors. The functional variant rs1229984 in alcohol dehydrogenase 1B (ADH1B) has been associated at a genome-wide level with alcohol use disorders in diverse adult populations. However, few data are available regarding whether this variant influences early drinking behaviors and whether social context moderates this effect. This study examines the interplay between rs1229984 and peer drinking in the development of adolescent drinking milestones.
  
  
  METHODS
  One thousand five hundred and fifty European and African American individuals who had a full drink of alcohol before age 18 were selected from a longitudinal study of youth as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Cox proportional hazards regression, with G × E product terms in the final models, was used to study 2 primary outcomes during adolescence: age of first intoxication and age of first DSM-5 alcohol use disorder symptom.
  
  
  RESULTS
  The minor A allele of rs1229984 was associated with a protective effect for first intoxication (HR = 0.56, 95% CI 0.41 to 0.76) and first DSM-5 symptom (HR = 0.45, 95% CI 0.26 to 0.77) in the final models. Reporting that most or all best friends drink was associated with a hazardous effect for first intoxication (HR = 1.81, 95% CI 1.62 to 2.01) and first DSM-5 symptom (HR = 2.17, 95% 1.88 to 2.50) in the final models. Furthermore, there was a significant G × E interaction for first intoxication (p = 0.002) and first DSM-5 symptom (p = 0.01). Among individuals reporting none or few best friends drinking, the ADH1B variant had a protective effect for adolescent drinking milestones, but for those reporting most or all best friends drinking, this effect was greatly reduced.
  
  
  CONCLUSIONS
  Our results suggest that the risk factor of best friends drinking attenuates the protective effect of a well-established ADH1B variant for 2 adolescent drinking behaviors. These findings illustrate the interplay between genetic and environmental factors in the development of drinking milestones during adolescence.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Emily
authors.initials: E
authors.lastname: Olfson
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: John
authors.initials: J
authors.lastname: Nurnberger
authors.forename: Arpana
authors.initials: A
authors.lastname: Agrawal
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Bucholz
authors.forename: Laura A
authors.initials: LA
authors.lastname: Almasy
authors.forename: David
authors.initials: D
authors.lastname: Chorlian
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.forename: Victor M
authors.initials: VM
authors.lastname: Hesselbrock
authors.forename: John R
authors.initials: JR
authors.lastname: Kramer
authors.forename: Samuel
authors.initials: S
authors.lastname: Kuperman
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schuckit
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: Jen-Chyong
authors.initials: JC
authors.lastname: Wang
authors.forename: Leah
authors.initials: L
authors.lastname: Wetherill
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Foroud
authors.forename: John
authors.initials: J
authors.lastname: Rice
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
mesh_terms: D000293:Adolescent; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D019973:Alcohol-Related Disorders / Q000235:genetics / Q000523:psychology; D000437:Alcoholism / Q000235:genetics / Q000523:psychology; D000483:Alleles; D002648:Child; D018450:Disease Progression; D004327:Drinking Behavior; D005260:Female; D059647:Gene-Environment Interaction; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010379:Peer Group; D016016:Proportional Hazards Models; D012929:Psychological Distance; D012307:Risk Factors; D012931:Social Environment; D014481:United States; D055815:Young Adult
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase
keywords: Adolescent; Alcohol Dehydrogenase; Gene-Environment Interaction; Peer Drinking