A genome-wide association study of alcohol dependence.
Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10(-5), but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2, which encodes the GABA receptor alpha2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.
Bierut
Laura J
LJ
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA. bierutl@psychiatry.wustl.edu
Agrawal
Arpana
A
Bucholz
Kathleen K
KK
Doheny
Kimberly F
KF
Laurie
Cathy
C
Pugh
Elizabeth
E
Fisher
Sherri
S
Fox
Louis
L
Howells
William
W
Bertelsen
Sarah
S
Hinrichs
Anthony L
AL
Almasy
Laura
L
Breslau
Naomi
N
Culverhouse
Robert C
RC
Dick
Danielle M
DM
Edenberg
Howard J
HJ
Foroud
Tatiana
T
Grucza
Richard A
RA
Hatsukami
Dorothy
D
Hesselbrock
Victor
V
Johnson
Eric O
EO
Kramer
John
J
Krueger
Robert F
RF
Kuperman
Samuel
S
Lynskey
Michael
M
Mann
Karl
K
Neuman
Rosalind J
RJ
Nöthen
Markus M
MM
Nurnberger
John I
JI
Porjesz
Bernice
B
Ridinger
Monika
M
Saccone
Nancy L
NL
Saccone
Scott F
SF
Schuckit
Marc A
MA
Tischfield
Jay A
JA
Wang
Jen C
JC
Rietschel
Marcella
M
Goate
Alison M
AM
Rice
John P
JP
D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D016022:Case-Control Studies; D005190:Family; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics; D015203:Reproducibility of Results
C484841:GABRA2 protein, human; D011963:Receptors, GABA-A