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

Ajna Hamidovic*, Robert J. Goodloe, Taylor R. Young, Mindi A. Styn, Kenneth J. Mukamal, Helene Choquet, Jay L. Kasberger, Sarah G. Buxbaum, George J. Papanicolaou, Wendy White, Kelly Volcik, Bonnie Spring, Brian Hitsman, Daniel Levy, Eric Jorgenson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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) with a P value in FHS of 0.042. The top variants in FHS were rs12249562 in cubulin (P = 3.03 × 10) and rs9839267 near cholecystokinin (P = 3.05 × 10) 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.

Original languageEnglish (US)
Pages (from-to)206-210
Number of pages5
JournalJournal of clinical psychopharmacology
Volume33
Issue number2
DOIs
StatePublished - Apr 2013

Keywords

  • alcohol consumption
  • alcoholism
  • cholecystokinin
  • methylenetetrahydrofolate dehydrogenase

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

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