Association between GABRA1 and drinking behaviors in the collaborative study on the genetics of alcoholism sample.
BACKGROUND
A wealth of literature supports the role of gamma-aminobutyric acid (GABA) in neurobiological pathways contributing to alcohol dependence and related phenotypes. Animal studies have consistently tied rodent homologs of the GABAA receptor genes on human chromosome 5q to alcohol-related behaviors; however, human studies have produced mixed results. Family-based association analyses previously conducted in the Collaborative Study on the Genetics of Alcoholism (COGA) sample yielded no evidence of association with Diagnostic and Statistical Manual of Mental Disorder-fourth edition (DSM-IV) alcohol dependence and these genes. As a follow-up to that study, we examined several alcohol-related behaviors in the COGA sample as follows: (1) a broader definition of alcohol dependence, including DSM-III-R symptoms and Feighner criteria (referred to as COGA alcohol dependence); (2) withdrawal; (3) history of alcohol-induced blackouts; (4) level of response to alcohol; (5) age of onset of regular drinking; and (6) age at first drunkenness.


METHODS
Family-based association tests were conducted, using multiple single-nucleotide polymorphisms (SNPs) in each of the 4 GABAA receptor genes on chromosome 5q.


RESULTS
In GABRA1, we found evidence of association with several of the drinking behavior phenotypes, including COGA alcohol dependence, history of blackouts, age at first drunkenness, and level of response to alcohol. We did not find consistent evidence of association with the remaining genes and any of the phenotypes.


CONCLUSIONS
We found evidence for association between GABRA1 and COGA alcohol dependence, history of blackouts, age at first drunkenness, and level of response to alcohol. These analyses suggest that efforts to characterize genetic contributions to alcohol dependence may benefit by examining alcohol-related behaviors in addition to clinical alcohol dependence diagnoses.
Dick
Danielle M
DM
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. dickd@wustl.edu
Plunkett
Jevon
J
Wetherill
Leah Flury
LF
Xuei
Xiaoling
X
Goate
Alison
A
Hesselbrock
Victor
V
Schuckit
Marc
M
Crowe
Raymond
R
Edenberg
Howard J
HJ
Foroud
Tatiana
T
D017668:Age of Onset; D000428:Alcohol Drinking / Q000235:genetics*; D000435:Alcoholic Intoxication / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011963:Receptors, GABA-A / Q000235:genetics*
C546240:GABRA1 protein, human; D011963:Receptors, GABA-A