Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites.
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY(2013)
摘要
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 x 10(-05)) with a P value in FHS of 0.042. The top variants in FITS were rs12249562 in cubulin (P = 3.03 x 10(-05)) and rs9839267 near chole-cystoldnin (P = 3.05 x 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.
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关键词
alcohol consumption,alcoholism,cholecystokinin,methylenetetrahydrofolate dehydrogenase
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