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Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites.
Thursday,2013-02-28 12:30 America/Los_Angeles — eenright
| Title | Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Hamidovic, 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, Jorgenson, E |
| Journal | J Clin Psychopharmacol |
| Volume | 33 |
| Issue | 2 |
| Start Page | 206 |
| Pagination | 206-10 |
| Date Published | 2013 Apr |
| ISSN | 1533-712X |
| Keywords | Aged, 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 | <p>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.</p> |
| DOI | 10.1097/JCP.0b013e318287009a |
| Alternate Journal | J Clin Psychopharmacol |
| PubMed ID | 23422394 |
| PubMed Central ID | PMC4339794 |
| Grant List | F32 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 |
ePub date:
2013-02-14