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

J Clin Psychopharmacol. 2013 Apr;33(2):206-10. doi: 10.1097/JCP.0b013e318287009a.

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Alcohol Drinking / epidemiology
  • Alcohol Drinking / genetics*
  • Alcoholism / diagnosis
  • Alcoholism / genetics*
  • Case-Control Studies
  • Feasibility Studies
  • Genetic Association Studies / methods
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Risk
  • White People / genetics*