An ADH1B variant and peer drinking in progression to adolescent drinking milestones

Evidence of a gene-by-environment interaction

Emily Olfson, Howard J. Edenberg, John Nurnberger, Arpana Agrawal, Kathleen K. Bucholz, Laura A. Almasy, David Chorlian, Danielle M. Dick, Victor M. Hesselbrock, John R. Kramer, Samuel Kuperman, Bernice Porjesz, Marc A. Schuckit, Jay A. Tischfield, Jen Chyong Wang, Leah Wetherill, Tatiana M. Foroud, John Rice, Alison Goate, Laura J. Bierut

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2541-2549
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume38
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

Fingerprint

Gene-Environment Interaction
Alcohol Dehydrogenase
Drinking
Genes
Alcohols
Drinking Behavior
Public health
Hazards
Adolescent Behavior
African Americans
Alcoholism
Longitudinal Studies
Public Health
Alleles
Underage Drinking
Genome
Population

Keywords

  • Adolescent
  • Alcohol Dehydrogenase
  • Gene-Environment Interaction
  • Peer Drinking

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

An ADH1B variant and peer drinking in progression to adolescent drinking milestones : Evidence of a gene-by-environment interaction. / Olfson, Emily; Edenberg, Howard J.; Nurnberger, John; Agrawal, Arpana; Bucholz, Kathleen K.; Almasy, Laura A.; Chorlian, David; Dick, Danielle M.; Hesselbrock, Victor M.; Kramer, John R.; Kuperman, Samuel; Porjesz, Bernice; Schuckit, Marc A.; Tischfield, Jay A.; Wang, Jen Chyong; Wetherill, Leah; Foroud, Tatiana M.; Rice, John; Goate, Alison; Bierut, Laura J.

In: Alcoholism: Clinical and Experimental Research, Vol. 38, No. 10, 01.10.2014, p. 2541-2549.

Research output: Contribution to journalArticle

Olfson, E, Edenberg, HJ, Nurnberger, J, Agrawal, A, Bucholz, KK, Almasy, LA, Chorlian, D, Dick, DM, Hesselbrock, VM, Kramer, JR, Kuperman, S, Porjesz, B, Schuckit, MA, Tischfield, JA, Wang, JC, Wetherill, L, Foroud, TM, Rice, J, Goate, A & Bierut, LJ 2014, 'An ADH1B variant and peer drinking in progression to adolescent drinking milestones: Evidence of a gene-by-environment interaction', Alcoholism: Clinical and Experimental Research, vol. 38, no. 10, pp. 2541-2549. https://doi.org/10.1111/acer.12524
Olfson, Emily ; Edenberg, Howard J. ; Nurnberger, John ; Agrawal, Arpana ; Bucholz, Kathleen K. ; Almasy, Laura A. ; Chorlian, David ; Dick, Danielle M. ; Hesselbrock, Victor M. ; Kramer, John R. ; Kuperman, Samuel ; Porjesz, Bernice ; Schuckit, Marc A. ; Tischfield, Jay A. ; Wang, Jen Chyong ; Wetherill, Leah ; Foroud, Tatiana M. ; Rice, John ; Goate, Alison ; Bierut, Laura J. / An ADH1B variant and peer drinking in progression to adolescent drinking milestones : Evidence of a gene-by-environment interaction. In: Alcoholism: Clinical and Experimental Research. 2014 ; Vol. 38, No. 10. pp. 2541-2549.
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T1 - An ADH1B variant and peer drinking in progression to adolescent drinking milestones

T2 - Evidence of a gene-by-environment interaction

AU - Olfson, Emily

AU - Edenberg, Howard J.

AU - Nurnberger, John

AU - Agrawal, Arpana

AU - Bucholz, Kathleen K.

AU - Almasy, Laura A.

AU - Chorlian, David

AU - Dick, Danielle M.

AU - Hesselbrock, Victor M.

AU - Kramer, John R.

AU - Kuperman, Samuel

AU - Porjesz, Bernice

AU - Schuckit, Marc A.

AU - Tischfield, Jay A.

AU - Wang, Jen Chyong

AU - Wetherill, Leah

AU - Foroud, Tatiana M.

AU - Rice, John

AU - Goate, Alison

AU - Bierut, Laura J.

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N2 - 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.

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