title: Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites.
abstract: Genetic association studies thus far have used detailed diagnoses of alcoholism to identify loci associated with risk. This proof-of-concept analysis examined whether population data of lifetime heaviest alcohol consumption may be used to identify genetic loci that modulate risk. We conducted a genetic association study in European Americans between variants in approximately 2100 genes and alcohol consumption as part of the Candidate gene Association Resource project. We defined cases as individuals with a history of drinking 5 or more drinks per day almost every day of the week and controls as current light drinkers (1-5 drinks per week). We cross-validated identified single nucleotide polymorphisms in a meta-analysis of 2 cohorts of unrelated individuals--Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)--and in a separate cohort of related individuals--Framingham Heart Study (FHS). The most significant variant in the meta-analysis of ARIC and CHS was rs6933598 in methylenetetrahydrofolate dehydrogenase (P = 7.46 × 10(-05)) with a P value in FHS of 0.042. The top variants in FHS were rs12249562 in cubulin (P = 3.03 × 10(-05)) and rs9839267 near cholecystokinin (P = 3.05 × 10(-05)) with a P value of 0.019 for rs9839267 in CHS. We have here shown feasibility in evaluating lifetime incidence of heavy alcohol drinking from population-based studies for the purpose of conducting genetic association analyses.
authors: Preventive Medicine, Northwestern University, Chicago, IL 60611-4402, USA. a-hamidovic@northwestern.edu
authors: Ajna
authors: A
authors: Hamidovic
authors: Robert J
authors: RJ
authors: Goodloe
authors: Taylor R
authors: TR
authors: Young
authors: Mindi A
authors: MA
authors: Styn
authors: Kenneth J
authors: KJ
authors: Mukamal
authors: Helene
authors: H
authors: Choquet
authors: Jay L
authors: JL
authors: Kasberger
authors: Sarah G
authors: SG
authors: Buxbaum
authors: George J
authors: GJ
authors: Papanicolaou
authors: Wendy
authors: W
authors: White
authors: Kelly
authors: K
authors: Volcik
authors: Bonnie
authors: B
authors: Spring
authors: Brian
authors: B
authors: Hitsman
authors: Daniel
authors: D
authors: Levy
authors: Eric
authors: E
authors: Jorgenson
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics*; D000437:Alcoholism / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005240:Feasibility Studies; D056726:Genetic Association Studies / Q000379:methods; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics*