No Linkage Between D2 Dopamine Receptor Gene Region and Schizophrenia

Hans W. Moises, Joel Gelernter, Luis A. Giuffra, Vincent Zarcone, Lennart Wetterberg, Olivier Civelli, Kenneth K. Kidd, Luca L. Cavalli Sforza, David K. Grandy, James L. Kennedy, Sophia Vinogradov, John Mauer, Michael Litt, Barbro Sjögren

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    94 Scopus citations

    Abstract

    • The dopamine hypothesis is one of the major etiological hypotheses of schizophrenia. The well-established role of genetic factors in schizophrenia together with reports of increased D2 dopamine receptor densities in untreated schizophrenic patients support the D2 dopamine receptor gene as a strong candidate gene for schizophrenia. The recent cloning of the D2 dopamine receptor gene made it possible to test the involvement of the D2 dopamine receptor locus (DRD2) in a large Swedish and a smaller Californian schizophrenia pedigree. Using multipoint linkage analysis between schizophrenia and a genetic map that includes the DRD2 locus and assuming a dominant mode of inheritance, we were able to exclude the DRD2 locus with a lod score of — 4.14 for the penetrance of 0.72 and with a lod score of — 3.05 for the lower bound penetrance of O.56. The area of exclusion (lod score, < — 2.00) extended 27 centimorgans. These results provide strong evidence against linkage of the D2 dopamine receptor gene region to schizophrenia in the two pedigrees investigated. We conclude that the genetic predisposition to schizophrenia in these pedigrees is not due to aberrations in the DRD2 locus or the porphobilinogen deaminase locus. Our results do not support the D2 dopamine receptor hypothesis of schizophrenia. However, they cannot exclude the possibility that other genes regulating aspects of D2 dopamine expression might be involved in the etiology of schizophrenia, such as the expression of two D2 dopamine receptor subtypes by alternative RNA splicing.

    Original languageEnglish (US)
    Pages (from-to)643-647
    Number of pages5
    JournalArchives of General Psychiatry
    Volume48
    Issue number7
    DOIs
    StatePublished - Jul 1991

    ASJC Scopus subject areas

    • Arts and Humanities (miscellaneous)
    • Psychiatry and Mental health

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  • Cite this

    Moises, H. W., Gelernter, J., Giuffra, L. A., Zarcone, V., Wetterberg, L., Civelli, O., Kidd, K. K., Cavalli Sforza, L. L., Grandy, D. K., Kennedy, J. L., Vinogradov, S., Mauer, J., Litt, M., & Sjögren, B. (1991). No Linkage Between D2 Dopamine Receptor Gene Region and Schizophrenia. Archives of General Psychiatry, 48(7), 643-647. https://doi.org/10.1001/archpsyc.1991.01810310061011