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

TitleGenetic analysis of a population heavy drinking phenotype identifies risk variants in whites.
Publication TypeJournal Article
Year of Publication2013
AuthorsHamidovic A, Goodloe RJ, Young TR, Styn MA, Mukamal KJ, Choquet H, Kasberger JL, Buxbaum SG, Papanicolaou GJ, White W, Volcik K, Spring B, Hitsman B, Levy D
Secondary AuthorsJorgenson E
JournalJ Clin Psychopharmacol
Volume33
Issue2
Pagination206-10
Date Published2013 Apr
ISSN1533-712X
KeywordsAged, Alcohol Drinking, Alcoholism, Case-Control Studies, European Continental Ancestry Group, Feasibility Studies, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Humans, Incidence, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Risk
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.

DOI10.1097/JCP.0b013e318287009a
Alternate JournalJ Clin Psychopharmacol
PubMed ID23422394
PubMed Central IDPMC4339794
Grant ListF32 DA024920 / DA / NIDA NIH HHS / United States
KL2 RR024130 / RR / NCRR NIH HHS / United States
ZIA HL006001-08 / / Intramural NIH HHS / United States
HHSN268200960009C / / PHS HHS / United States
R21 AA021223-01 / AA / NIAAA NIH HHS / United States
Z01 HL006001-02 / / Intramural NIH HHS / United States
P20 MD006899 / MD / NIMHD NIH HHS / United States
ZIA HL006001-04 / / Intramural NIH HHS / United States
ZIA HL006001-06 / / Intramural NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States
F32DA024920 / DA / NIDA NIH HHS / United States
R21 AA021223 / AA / NIAAA NIH HHS / United States
ZIA HL006001-07 / / Intramural NIH HHS / United States
Z99 HL999999 / / Intramural NIH HHS / United States
Z01 HL006001-01 / / Intramural NIH HHS / United States
ZIA HL006001-03 / / Intramural NIH HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States