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Molecular Psychiatry
  • Original Article
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ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry

Molecular Psychiatryvolume 17, pages445–450 (2012)Cite this article

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), withP=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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Acknowledgements

Support for the Collaborative Study on the Genetics of Alcoholism (COGA) was provided by the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse (U10 AA008401). Support for the Collaborative Genetic Study of Nicotine Dependence (COGEND) was provided by the National Cancer Institute (P01 CA089392). Support for the Family Study of Cocaine Dependence (FSCD) was provided by the National Institute on Drug Abuse (R01 DA013423, R01 DA019963). This work was also supported by NIDA Grant K02 DA021237 to LJB. A detailed list of acknowledgments and funding sources can be found in the Supplementary Information online. We thank Sherri Fisher for her organization and assistance in the development of this manuscript.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA

    L J Bierut, A M Goate, S Bertelsen, L Fox, A Agrawal, K K Bucholz, R Grucza, J C Wang & J P Rice

  2. Department of Epidemiology, Michigan State University, East Lansing, MI, USA

    N Breslau

  3. Division of Health, Social and Economic Research, Research Triangle Institute International, Research Triangle Park, NC, USA

    E O Johnson

  4. Department of Psychiatry, University of Connecticut, Farmington, CT, USA

    V Hesselbrock

  5. Department of Psychiatry, University of Iowa, Iowa City, IA, USA

    J Kramer

  6. Division of Child Psychiatry, University of Iowa Hospitals, Iowa City, IA, USA

    S Kuperman

  7. Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA

    J Nurnberger

  8. Department of Psychiatry, State University of New York, Brooklyn, NY, USA

    B Porjesz

  9. Department of Genetics, Washington University School of Medicine, St Louis, MO, USA

    N L Saccone

  10. Department of Psychiatry, University of California-San Diego, La Jolla, CA, USA

    M Schuckit

  11. Department of Genetics, Rutgers University, Piscataway, NJ, USA

    J Tischfield

  12. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA

    T Foroud & H J Edenberg

  13. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    H J Edenberg

Authors
  1. L J Bierut
  2. A M Goate
  3. N Breslau
  4. E O Johnson
  5. S Bertelsen
  6. L Fox
  7. A Agrawal
  8. K K Bucholz
  9. R Grucza
  10. V Hesselbrock
  11. J Kramer
  12. S Kuperman
  13. J Nurnberger
  14. B Porjesz
  15. N L Saccone
  16. M Schuckit
  17. J Tischfield
  18. J C Wang
  19. T Foroud
  20. J P Rice
  21. H J Edenberg

Corresponding author

Correspondence toL J Bierut.

Ethics declarations

Competing interests

Dr Bierut, Dr Rice, Dr Goate and Dr Wang are inventors on the patent ‘Markers for Addiction’ (US 20070258898) covering the use of certain SNPs in determining the diagnosis, prognosis and treatment of addiction. Dr NL Saccone is the spouse of Dr S Saccone, who is listed as an inventor on the patent. Dr Bierut served as a consultant for Pfizer Inc. in 2008. Dr Breslau, Dr Johnson, Ms Bertelsen, Mr Fox, Dr Agrawal, Dr Bucholz, Dr Grucza, Dr Hesselbrock, Dr Kramer, Dr Nurnberger, Dr Porjesz, Dr Schuckit, Dr Tischfield, Dr Foroud and Dr Edenberg declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Molecular Psychiatry website

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Bierut, L., Goate, A., Breslau, N.et al.ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.Mol Psychiatry17, 445–450 (2012). https://doi.org/10.1038/mp.2011.124

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