title: ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.
abstract: A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA. laura@wustl.edu
authors.forename: L J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: A M
authors.initials: AM
authors.lastname: Goate
authors.forename: N
authors.initials: N
authors.lastname: Breslau
authors.forename: E O
authors.initials: EO
authors.lastname: Johnson
authors.forename: S
authors.initials: S
authors.lastname: Bertelsen
authors.forename: L
authors.initials: L
authors.lastname: Fox
authors.forename: A
authors.initials: A
authors.lastname: Agrawal
authors.forename: K K
authors.initials: KK
authors.lastname: Bucholz
authors.forename: R
authors.initials: R
authors.lastname: Grucza
authors.forename: V
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: J
authors.initials: J
authors.lastname: Kramer
authors.forename: S
authors.initials: S
authors.lastname: Kuperman
authors.forename: J
authors.initials: J
authors.lastname: Nurnberger
authors.forename: B
authors.initials: B
authors.lastname: Porjesz
authors.forename: N L
authors.initials: NL
authors.lastname: Saccone
authors.forename: M
authors.initials: M
authors.lastname: Schuckit
authors.forename: J
authors.initials: J
authors.lastname: Tischfield
authors.forename: J C
authors.initials: JC
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Foroud
authors.forename: J P
authors.initials: JP
authors.lastname: Rice
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase