Association of GABA(A) receptors and alcohol dependence and the effects of genetic imprinting.
GABA receptor genes have been postulated as candidates affecting the risk for alcoholism. The potential association between genes encoding five subunits of the GABA(A) 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 GABA(A)-gene cluster on chromosome 15 and alcoholism that is modulated by genetic imprinting.
Song
Jiuzhou
J
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, Indiana 46202-5122, USA.
Koller
Daniel L
DL
Foroud
Tatiana
T
Carr
Kristie
K
Zhao
Jinghua
J
Rice
John
J
Nurnberger
John I
JI
Begleiter
Henri
H
Porjesz
Bernice
B
Smith
Tom L
TL
Schuckit
Marc A
MA
Edenberg
Howard J
HJ
D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D002884:Chromosomes, Human, Pair 15; D018392:Genomic Imprinting / Q000502:physiology*; D006801:Humans; D015810:Linkage Disequilibrium; D010375:Pedigree; D021122:Protein Subunits / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics*
D021122:Protein Subunits; D011963:Receptors, GABA-A