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Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites.

Research paper by Ajna A Hamidovic, Robert J RJ Goodloe, Taylor R TR Young, Mindi A MA Styn, Kenneth J KJ Mukamal, Helene H Choquet, Jay L JL Kasberger, Sarah G SG Buxbaum, George J GJ Papanicolaou, Wendy W White, Kelly K Volcik, Bonnie B Spring, Brian B Hitsman, Daniel D Levy, Eric E Jorgenson

Indexed on: 21 Feb '13Published on: 21 Feb '13Published in: Journal of clinical psychopharmacology



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.