A genome-wide association study of alcohol dependence

被引：343

作者：

Bierut, Laura J. ^{[1
]}

Agrawal, Arpana ^{[1
]}

Bucholz, Kathleen K. ^{[1
]}

Doheny, Kimberly F. ^{[2
]}

Laurie, Cathy ^{[3
]}

Pugh, Elizabeth ^{[2
]}

Fisher, Sherri ^{[1
]}

Fox, Louis ^{[1
]}

Howells, William ^{[1
]}

Bertelsen, Sarah ^{[1
]}

Hinrichs, Anthony L. ^{[1
]}

Almasy, Laura ^{[4
]}

Breslau, Naomi ^{[5
]}

Culverhouse, Robert C. ^{[6
]}

Dick, Danielle M. ^{[7
]}

Edenberg, Howard J. ^{[8
]}

Foroud, Tatiana ^{[9
]}

Grucza, Richard A. ^{[1
]}

Hatsukami, Dorothy ^{[10
]}

Hesselbrock, Victor ^{[11
]}

Johnson, Eric O. ^{[12
]}

Kramer, John ^{[13
]}

Krueger, Robert F. ^{[1
]}

Kuperman, Samuel ^{[14
]}

Lynskey, Michael ^{[1
]}

Mann, Karl ^{[15
]}

Neuman, Rosalind J. ^{[1
]}

Noethen, Markus M. ^{[16
]}

Nurnberger, John I., Jr. ^{[17
]}

Porjesz, Bernice ^{[18
]}

Ridinger, Monika ^{[19
]}

Saccone, Nancy L. ^{[20
]}

Saccone, Scott F. ^{[1
]}

Schuckit, Marc A. ^{[21
]}

Tischfield, Jay A. ^{[22
]}

Wang, Jen C. ^{[1
]}

Rietschel, Marcella ^{[23
]}

Goate, Alison M. ^{[1
]}

Rice, John P. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[2] Johns Hopkins Med Ctr, Ctr Inherited Dis Res, Baltimore, MD 21224 USA

[3] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[4] SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA

[5] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA

[6] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[7] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA

[8] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

[9] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

[10] Univ Minnesota, Tobacco Res Ctr, Minneapolis, MN 55415 USA

[11] Univ Connecticut, Dept Psychiat, Farmington, CT 06030 USA

[12] Res Triangle Inst Int, Div Hlth Social & Econ Res, Res Triangle Pk, NC 27709 USA

[13] Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA

[14] Univ Iowa Hosp, Div Child Psychiat, Iowa City, IA 52242 USA

[15] Cent Inst Mental Hlth, Dept Addict Behav & Addict Med, D-6800 Mannheim, Germany

[16] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany

[17] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA

[18] SUNY, Dept Psychiat, Brooklyn, NY 11203 USA

[19] Univ Regensburg, Mental State Hosp, Dept Psychiat, Regensburg, Germany

[20] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[21] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA

[22] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA

[23] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 11期

基金：

美国国家卫生研究院;

关键词：

genetics; candidate genes; ENVIRONMENTAL CONTRIBUTIONS; NICOTINE DEPENDENCE; LINKAGE DISEQUILIBRIUM; FAMILIAL TRANSMISSION; RISK-FACTORS; GABRA2; GENE; MALE TWINS; DRUG-USE; RECEPTOR; POPULATION;

D O I：

10.1073/pnas.0911109107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 alpha 2 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.

引用

页码：5082 / 5087

页数：6

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