Skip to main content
Log in

Why there is no gene for alcoholism

  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

The search for and recognition of biological and genetic markers of alcoholism are discussed in the context of a heuristic model of human alcoholism as a complex, multilocus, heterogeneous disorder. Implications of this model for the interpretation of results from both linkage and association studies are presented.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alexopoulos, G. S., Lieberman, K. W., Frances, R., and Stokes, P. E. (1981). Platelet MAO during the alcohol withdrawal syndrome.Am. J. Psychiat. 138:1254–1255.

    Google Scholar 

  • Anokina, I. P., Kogan, B. M., Nickel, B., Schultz, R., and Kemper, A. (1989). Basal activities of adenylate and guanylate cyclase in lymphocytes and platelets of alcoholics.Biomed. Biochim. Acta 48:593–596.

    Google Scholar 

  • Blum, K., Noble, E. P., Sheridan, P. J., Montgomery, A., Ritchie, T., Jagadeeswaran, P., Nogami, H., Briggs, A. H., and Cohn, J. B. (1990). Allelic association of human dopamine D2 receptor gene in alcoholism.JAMA 263:2055–2060.

    Google Scholar 

  • Blum, K., Noble, E. P., Sheridan, P. J., Finley, O., Montgomery, A., Ritchie, T., Ozkaragoy, T., Fitch, R. J., Sadlack, F., Sheffield, D., Dahlmann, T., Halbardier, S., and Nogami, H. (1991). Association of the A1 allele of the D2 dopamine receptor gene.Alcohol 8:409–416.

    Google Scholar 

  • Bolos, A. M., Dean, M., Lucas-Derse, S., Ramsburg, M., Brown, G. L., and Goldman, D. (1990). Population and pedigree studies reveal lack of association between the dopamine D2 receptor gene and alcoholism.JAMA 264:3156–3160.

    Google Scholar 

  • Botstein, D., White, R. L., Skolnick, M., and Davis, R. W. (1980). Construction of a genetic linkage map in man using restriction fragment length polymorphisms.Am. J. Hum. Genet. 32:314–331.

    Google Scholar 

  • Clerget-Darpoux, F., Bonaiti-Pellie, C., and Hocheny, J. (1986). Effects of misspecifying genetic parameters in lod score analysis.Biometrics 42:393–399.

    Google Scholar 

  • Cloninger, C. R. (1987). Neurogenetic adaptive mechanisms in alcoholism.Science 236:410–416.

    Google Scholar 

  • Cloninger, C. R. (1991). D2 dopamine receptor gene is associated but not linked with alcoholismJAMA 266:1833–1834.

    Google Scholar 

  • Comings, D. E., Comings, B. G., Muhleman, D., Dietz, G., Shahbahrami, B., Tast, D., Knell, E., Kocsis, P., Baumgarten, R., Kovacs, B. W., Levy, D. L., Smith, M., Borison, R. L., Evans, D. D., Klein, D. N., MacMurray, J., Tosk, J. J., Sverd, J., Gysin, R., and Flanigan, S. D. (1991). The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders.JAMA 266:1793–1800.

    Google Scholar 

  • Conneally, P. M. (1989). Criteria for optimal linkage studies in alcoholism. In Kuanmaa, T., Tabakoff, B., and Saito, T. (eds.),Genetic Aspects of Alcoholism, Finn Found. Alc. Stud., Helsinki, pp. 259–264.

    Google Scholar 

  • Crabb, D. W., Edenberg, H. J., Bosron, W. F., and Li, T.-K. (1989). Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity.J. Clin. Invest. 83:314–316.

    Google Scholar 

  • Devor, E. J., and Cloninger, C. R. (1989). Genetics of alcoholism.Annu. Rev. Genet. 23:19–36.

    Google Scholar 

  • Devor, E. J., Cloninger, C. R., Hoffman, P. L., and Tabakoff, B. (1991). A genetic study of platelet adenylate cyclase activity: Evidence for a single major locus effect in fluoride-stimulated activity.Am. J. Hum. Genet. 49:372–377.

    Google Scholar 

  • Devor, E. J., Cloninger, C. R., Hoffman, P. L., and Tabakoff, B. (1992a). Association of monoamine oxidase (MAO) activity with alcoholism and alcoholic subtypes (submitted for publication).

  • Devor, E. J., Cloninger, C. R., Kwan, S.-W., and Abell, C. W. (1992b). A genetic/familial study of monoamine oxidase B activity and concentration in alcoholics.Alcohol. Clin. Exp. Res. (in press).

  • Diamond, I., Wrubel, B., Estrin, W., and Gordon, A. (1987). Basal and adenosine receptor-stimulated levels of cyclic AMP are reduced in lymphocytes from alcoholic receptor-stimulated levels of cyclic AMP are reduced in lymphocytes from alcoholic patients.Proc. Natl. Acad. Sci. USA 84:1413–1416.

    Google Scholar 

  • Dorchester, D. (1884).The Liquor Problem in All Ages, Phillips and Hunt, New York.

    Google Scholar 

  • Faraj, B. A., Lenton, J. D., Kutner, M., Camp, V. M., Stammers, T. W., Lee, S. R., Lolies, P. A., and Chandora, D. (1987). Prevalence of low monoamine oxidase function in alcoholism.Alcohol. Clin. Exp. Res. 11:464–467.

    Google Scholar 

  • Gelernter, J., O'Malley, S., Risch, N., Kranzler, H. R., Krystal, J., Merikangas, K., Kennedy, J. L., and Kidd, K. K. (1991). No association between an allele at the D2 dopamine receptor gene (DRD2) and alcoholism.JAMA 266:1801–1807.

    Google Scholar 

  • Gilligan, S. B., Reich, T., and Cloninger, C. R. (1987). Etiologic heterogeneity in alcoholism.Genet. Epidemiol. 4:395–414.

    Google Scholar 

  • Goedde, H. W., Singh, S., Agarwal, D. P., Fritze, G., Stapel, K., and Paik, Y. K. (1989). Genotyping of mitochondrial aldehyde dehydrogenase in blood samples using allele-specific oligonucleotides: Comparison with phenotyping hair roots.Hum. Genet. 81:305–307.

    Google Scholar 

  • Goodwin, D. W., and Guze, S. B. (1989).Psychiatric Diagnosis, 4th ed., Oxford University Press, Oxford.

    Google Scholar 

  • Gusella, J. F., Wexler, N. S., Conneally, P. M., Naylor, S. L., Anderson, M. A., Tanzi, R. E., Watkins, P. C., Ottina, K., Wallace, M. R., Sakaguchi, A. Y., Young, A. B., Shoulson, I., Bonilla, E., and Martin, J. D. (1983). A polymorphic DNA marker genetically linked to Huntington's disease.Nature 306:234–238.

    Google Scholar 

  • Gustafson, A. (1987).The Foundation of Death: A Study of the Drink Question, Funk and Wagnalls, New York.

    Google Scholar 

  • Harada, S., Agarwal, D. P., Goedde, H., Togzki, S., and Ishikawa, B. (1982). Possible protective role against alcoholism for aldehyde dehydrogenase isozyme deficiency in Japan.Lancet. 2:827.

    Google Scholar 

  • Harada, S., Agarwal, D. P., Goedde, H. W., and Ishikawa, B. (1983). Aldehyde dehydrogenase isozyme variation and alcoholism in Japan.Pharmacol. Biochem. Behav. 18 (Suppl. 1):151–153.

    Google Scholar 

  • Harada, S., Agarwal, D. P., and Goedde, H. W. (1985). Aldehyde dehydrogenase polymorphism and alcohol metabolism in alcoholics.Alcohol 2:391–392.

    Google Scholar 

  • Itoh, H., and Gilman, A. G. (1991). Expression and analysis of Gαs mutants with decreased ability to activate adenylylcyclase.J. Biol. Chem. 266:16226–16231.

    Google Scholar 

  • Kochersperger, L. M., Parker, E. L., Sicliano, M., Darlington, G. J., and Denney, R. M. (1986). Assignment of genes for human monoamine oxidase A and B to the X chromosome.J. Neurosci. Res. 16:601–616.

    Google Scholar 

  • Lan, N. C., Heinzmann, C., Gal, A., Klisak, I., Orth, V., Lai, E., Grimsby, J., Sparkes, R. S., Mohandas, T., and Shih, J. C. (1989). Human monoamine oxidase A and B genes map to Xp11.23 and are deleted in a patient with Norrie disease.Genomics 5:552–559.

    Google Scholar 

  • Major, L. F., Goyer, P. F., and Murphy, D. L. (1981). Changes in platelet monoamine oxidase activity during abstinence.J. Stud. Alcohol. 42:1052–1057.

    Google Scholar 

  • Mizoi, Y., Kogame, M., Jukanaga, T., Veno, Y., Adachi, J., and Fujiwara, S. (1985). Polymorphism of aldehyde dehydrogenase and ethanol elimination.Alcohol 2:393–396.

    Google Scholar 

  • Monaco, A., Neve, R., Colletti-Feener, C., Bertelson, C., Kurmit, D., and Kunkel, L. (1986). Isolation of the candidate cDNAs for portions of the Duchenne muscular dystrophy gene.Nature 323:646–650.

    Google Scholar 

  • Nakamura, Y., Leppert, M., O'Connell, P., Wolff, R., Holm, T., Culver, M., Martin, C., Fujimoto, E., Hoff, M., Kumlin, E., and White, R. (1987). Variable number of tandem repeat (VNTR) markers for human gene mapping.Science 235:1616–1622.

    Google Scholar 

  • Ozawa, H., Katamura, Y., Ashizawa, T., Watanake, M., Hatta, S., Takahata, N., and Saito, T. (1992). Platelet adenylate cyclase activity in long-term abstinent alcoholics.Alcohol. Alcohol. 27 (Suppl. 1):69.

    Google Scholar 

  • Pandy, G. N., Fawcett, J., Gibbons, R., Clark, D. C., and Davis, J. M. (1988). Platelet monoamine oxidase in alcoholism.Biol. Psychiat. 24:15–24.

    Google Scholar 

  • Parsian, A., Todd, R. D., Devor, E. J., O'Malley, K. L., Suarez, B. K., Reich, T., and Cloninger, C. R. (1991). Alcoholism and alleles of the human D2 dopamine receptor locus.Arch. Gen. Psychiat. 48:655–663.

    Google Scholar 

  • Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmakel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsik, N., Chou, J.-L., Drumm, M. L., Iannuzzi, M. C., Goldins, F. S., and Tsui, L.-C. (1989). Identification of the cyctic fibrosis gene: Cloning and characterization of complementary DNA.Science 245:1066–1073.

    Google Scholar 

  • Risch, N. (1990). Genetic linkage and complex diseases with special reference to psychiatric disorders.Genet. Epidemiol. 7:3–16.

    Google Scholar 

  • Risch, N. (1992). Genetic linkage: Interpreting lod scores.Science 255:803–804.

    Google Scholar 

  • Risch, N., Claus, E., and Giuffra, L. (1989). Linkage and mode of inheritance in complex traits. In Elston, R. C., Spence, M. A., Hodge, S. E., and MacCluer, J. M. (eds.),Multipoint Mapping and Linkage Based upon Affected Pedigree Members, GAW6, Alan R. Liss, New York, pp. 183–188.

    Google Scholar 

  • Schuckit, M. A., Shaskan, E., Duby, J., Vega, R., and Moss, M. (1982). Platelet monoamine oxidase activity in relatives of alcoholics.Arch. Gen. Psychiat. 39:137–140.

    Google Scholar 

  • Smith, M. (1986). Genetics of human alcohol and aldehyde dehydrogenases.Adv. Hum. Genet. 15:249–290.

    Google Scholar 

  • Sournia, J.-C. (1990).History of Alcoholism (English translation), Blackwells, Oxford.

    Google Scholar 

  • Tabakoff, B., Hoffman, P. L., Lee, J. M., Saito, T., Willard, B., and DeLeon-Jones, F. (1988). Differences in platelet enzyme activity between alcoholics and non-alcoholics.N. Engl. J. Med. 318:134–139.

    Google Scholar 

  • Thomasson, H. R., Edenberg, H. J., Crabb, D. W., Mai, X.-L., Jerome, R. E., Li, T.-K., Wang, S.-P., Lin, Y.-T., Lu, R.-B., and Yin, S.-J. (1991). Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men.Am. J. Hum. Genet. 48:677–681.

    Google Scholar 

  • Tsukamoto, S., Muto, T., Nagoya, T., Shimamura, M., Saito, M., and Tainaka, H. (1989). Determinations of ethanol, acetaldehyde, and acetate in blood and uring during alcohol oxidation in man.Alcohol. Alcohol. 24:101–108.

    Google Scholar 

  • Uhl, G. R., Persico, A. M., and Smith, S. S. (1992). Current excitement with D2 dopamine receptor gene alleles in substance abuse.Arch. Gen. Psychiat. 49:157–160.

    Google Scholar 

  • Vieland, V. J., Hodge, S. E., and Greenberg, D. A. (1992). Adequacy of single-locus approximations for linkage-analyses of oligogenic traits.Genet. Epidemiol. 9:45–59.

    Google Scholar 

  • von Knorring, L., Oreland, L., and Winblad, B. (1984). Personality traits related to monoamine oxidase activity in platelets.Psychiat. Res. 12:11–26.

    Google Scholar 

  • von Knorring, A.-L., Bohman, M., von Knorring, L., and Oreland, L. (1985). Platelet MAO activity as a biological marker in subgroups of alcoholism.Acta Psychiat. Scand. 72:51–58.

    Google Scholar 

  • von Knorring, A.-L., Hallman, J., von Knorring, L., and Oreland, L. (1991). Platelet monoamine oxidase activity in Type I and Type 2 alcoholism.Alcohol. Alcohol. 26:409–416.

    Google Scholar 

  • Weber, J. L., and May, P. E. (1989). An abundant new class of human DNA polymorphisms which can be typed using the polymerase chain reaction.Am. J. Hum. Genet. 44:388–396.

    Google Scholar 

  • Wiberg, A., Gottfries, C.-G., and Oreland, L. (1977). Low platelet monoamine oxidase activity in human alcoholics.Med. Biol. 55:181–186.

    Google Scholar 

  • Wolff, P. H. (1972). Ethnic differences in alcohol sensitivity.Science 175:449–450.

    Google Scholar 

  • Yoshida, A., Huang, I.-Y., and Ikawa, M. (1984). Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals.Proc. Natl. Acad. Sci. USA 81:258–261.

    Google Scholar 

  • Yoshihara, H., Sato, N., Kamada, T., and Abe, H. (1983). Low Km ALDH isozyme and alcoholic liver injury.Pharmacol. Biochem. Behav. 18: (Suppl. 1):425–428.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Devor, E.J. Why there is no gene for alcoholism. Behav Genet 23, 145–151 (1993). https://doi.org/10.1007/BF01067419

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01067419

Key Words

Navigation