title: A genome-wide association study of alcohol dependence.
abstract: 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.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA. bierutl@psychiatry.wustl.edu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: Arpana
authors.initials: A
authors.lastname: Agrawal
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Bucholz
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Doheny
authors.forename: Cathy
authors.initials: C
authors.lastname: Laurie
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pugh
authors.forename: Sherri
authors.initials: S
authors.lastname: Fisher
authors.forename: Louis
authors.initials: L
authors.lastname: Fox
authors.forename: William
authors.initials: W
authors.lastname: Howells
authors.forename: Sarah
authors.initials: S
authors.lastname: Bertelsen
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Hinrichs
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Naomi
authors.initials: N
authors.lastname: Breslau
authors.forename: Robert C
authors.initials: RC
authors.lastname: Culverhouse
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Richard A
authors.initials: RA
authors.lastname: Grucza
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hatsukami
authors.forename: Victor
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: Eric O
authors.initials: EO
authors.lastname: Johnson
authors.forename: John
authors.initials: J
authors.lastname: Kramer
authors.forename: Robert F
authors.initials: RF
authors.lastname: Krueger
authors.forename: Samuel
authors.initials: S
authors.lastname: Kuperman
authors.forename: Michael
authors.initials: M
authors.lastname: Lynskey
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Neuman
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
authors.forename: Monika
authors.initials: M
authors.lastname: Ridinger
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Saccone
authors.forename: Scott F
authors.initials: SF
authors.lastname: Saccone
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schuckit
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: Jen C
authors.initials: JC
authors.lastname: Wang
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
mesh_terms: 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
chemical_list: C484841:GABRA2 protein, human; D011963:Receptors, GABA-A