Association of GABAA receptors and alcohol dependence and the effects of genetic imprinting

Jiuzhou Song, Daniel L. Koller, Tatiana Foroud, Kristie Carr, Jinghua Zhao, John Rice, John I. Nurnberger, Henri Begleiter, Bernice Porjesz, Tom L. Smith, Marc A. Schuckit, Howard J. Edenberg

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

GABA receptor genes have been postulated as candidates affecting the risk for alcoholism. The potential association between genes encoding five subunits of the GABAA receptors and alcoholism (alcohol dependence) was analyzed in the multiplex alcoholic pedigrees collected by the Collaborative Study on the Genetics of Alcoholism (COGA) using family-based association tests. We found consistent, although weak, linkage disequilibrium between GABRB1 (located on chromosome 4) and alcoholism (P < 0.03). Genes encoding GABRA1 and GABRA6, on chromosome 5, did not provide evidence for association with alcoholism. GABRA5 and GABRB3, on chromosome 15, were reported to be expressed uniparentally from the paternal chromosome. Analyses of paternal transmission of alleles of GABRA5 provided evidence for association with alcoholism, particularly in the Caucasian population and with the stricter ICD-10 definition of alcoholism (P < 0.004). Evidence of association was also observed during paternal transmission with GABRB3 in the Caucasian population (P < 0.007). Maternal transmissions provided no evidence for association. These data are consistent with an association between the expressed alleles in the GABAA-gene cluster on chromosome 15 and alcoholism that is modulated by genetic imprinting.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume117 B
Issue number1
DOIs
StatePublished - Feb 15 2003

Keywords

  • Alcoholism
  • Gamma-aminobutyric acid receptor
  • Genetic association
  • Genetic imprinting

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