| A genome-wide association study of alcohol dependence. | |
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MedLine Citation:
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PMID: 20202923 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10(-5), but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2, which encodes the GABA receptor alpha2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence. |
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Authors:
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Laura J Bierut; Arpana Agrawal; Kathleen K Bucholz; Kimberly F Doheny; Cathy Laurie; Elizabeth Pugh; Sherri Fisher; Louis Fox; William Howells; Sarah Bertelsen; Anthony L Hinrichs; Laura Almasy; Naomi Breslau; Robert C Culverhouse; Danielle M Dick; Howard J Edenberg; Tatiana Foroud; Richard A Grucza; Dorothy Hatsukami; Victor Hesselbrock; Eric O Johnson; John Kramer; Robert F Krueger; Samuel Kuperman; Michael Lynskey; Karl Mann; Rosalind J Neuman; Markus M Nöthen; John I Nurnberger; Bernice Porjesz; Monika Ridinger; Nancy L Saccone; Scott F Saccone; Marc A Schuckit; Jay A Tischfield; Jen C Wang; Marcella Rietschel; Alison M Goate; John P Rice; |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-03-02 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-22 Completed Date: 2010-04-22 Revised Date: 2011-05-05 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 5082-7 Citation Subset: IM |
Affiliation:
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Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA. bierutl@psychiatry.wustl.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Alcoholism / genetics* Case-Control Studies Family Female Genome-Wide Association Study* Humans Male Odds Ratio Polymorphism, Single Nucleotide / genetics Receptors, GABA-A / genetics Reproducibility of Results |
| Grant Support | |
ID/Acronym/Agency:
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P01 CA089392/CA/NCI NIH HHS; P01 CA089392-07/CA/NCI NIH HHS; R01 DA013423/DA/NIDA NIH HHS; R01 DA013423-05/DA/NIDA NIH HHS; R01 DA019963-01A2/DA/NIDA NIH HHS; R01 DA019963-02/DA/NIDA NIH HHS; R01 DA019963-03/DA/NIDA NIH HHS; U01 HG004422/HG/NHGRI NIH HHS; U01 HG004422-02/HG/NHGRI NIH HHS; U01 HG004446/HG/NHGRI NIH HHS; U01HG004438/HG/NHGRI NIH HHS; U10 AA008401/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/GABRA2 protein, human; 0/Receptors, GABA-A |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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