ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry

L. J. Bierut, A. M. Goate, N. Breslau, E. O. Johnson, S. Bertelsen, L. Fox, A. Agrawal, K. K. Bucholz, R. Grucza, V. Hesselbrock, J. Kramer, S. Kuperman, John Nurnberger, B. Porjesz, N. L. Saccone, M. Schuckit, J. Tischfield, J. C. Wang, Tatiana Foroud, J. P. RiceHoward Edenberg

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10 -10). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10 -13. We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations.

Original languageEnglish
Pages (from-to)445-450
Number of pages6
JournalMolecular Psychiatry
Volume17
Issue number4
DOIs
StatePublished - Apr 2012

Fingerprint

Alcohol Dehydrogenase
Alcohol Drinking
Alcoholism
Population
Diagnostic and Statistical Manual of Mental Disorders
Alleles
Gene Frequency
African Americans
Case-Control Studies
Young Adult
Odds Ratio
Alcohols
Genome
Confidence Intervals

Keywords

  • ADH1B
  • alcohol dehydrogenase
  • alcohol dependence
  • association study
  • genetics
  • protective allele

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry. / Bierut, L. J.; Goate, A. M.; Breslau, N.; Johnson, E. O.; Bertelsen, S.; Fox, L.; Agrawal, A.; Bucholz, K. K.; Grucza, R.; Hesselbrock, V.; Kramer, J.; Kuperman, S.; Nurnberger, John; Porjesz, B.; Saccone, N. L.; Schuckit, M.; Tischfield, J.; Wang, J. C.; Foroud, Tatiana; Rice, J. P.; Edenberg, Howard.

In: Molecular Psychiatry, Vol. 17, No. 4, 04.2012, p. 445-450.

Research output: Contribution to journalArticle

Bierut, LJ, Goate, AM, Breslau, N, Johnson, EO, Bertelsen, S, Fox, L, Agrawal, A, Bucholz, KK, Grucza, R, Hesselbrock, V, Kramer, J, Kuperman, S, Nurnberger, J, Porjesz, B, Saccone, NL, Schuckit, M, Tischfield, J, Wang, JC, Foroud, T, Rice, JP & Edenberg, H 2012, 'ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry', Molecular Psychiatry, vol. 17, no. 4, pp. 445-450. https://doi.org/10.1038/mp.2011.124
Bierut, L. J. ; Goate, A. M. ; Breslau, N. ; Johnson, E. O. ; Bertelsen, S. ; Fox, L. ; Agrawal, A. ; Bucholz, K. K. ; Grucza, R. ; Hesselbrock, V. ; Kramer, J. ; Kuperman, S. ; Nurnberger, John ; Porjesz, B. ; Saccone, N. L. ; Schuckit, M. ; Tischfield, J. ; Wang, J. C. ; Foroud, Tatiana ; Rice, J. P. ; Edenberg, Howard. / ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry. In: Molecular Psychiatry. 2012 ; Vol. 17, No. 4. pp. 445-450.
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abstract = "A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95{\%} confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10 -10). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10 -13. We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations.",
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