A genome-wide association study of alcohol dependence
| Autor: | Howard J. Edenberg, Alison Goate, Richard A. Grucza, Nancy L. Saccone, Sherri L. Fisher, John I. Nurnberger, Scott F. Saccone, Samuel Kuperman, Victor Hesselbrock, Elizabeth W. Pugh, John Kramer, Anthony L. Hinrichs, William Howells, Arpana Agrawal, Karl Mann, Laura Almasy, Kimberly F. Doheny, Robert Culverhouse, Monika Ridinger, Louis Fox, Robert F. Krueger, Michael T. Lynskey, Marcella Rietschel, Dorothy K. Hatsukami, Eric O. Johnson, Tatiana Foroud, Markus M. Nöthen, Cathy C. Laurie, Marc A. Schuckit, Danielle M. Dick, Rosalind J. Neuman, Naomi Breslau, Bernice Porjesz, Jen C. Wang, Jay A. Tischfield, Kathleen K. Bucholz, Laura J. Bierut, John P. Rice, Sarah Bertelsen |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Genetics Candidate gene Multidisciplinary Alcohol dependence Case-control study Reproducibility of Results Single-nucleotide polymorphism Genome-wide association study Odds ratio Biological Sciences Biology Receptors GABA-A Polymorphism Single Nucleotide Alcoholism Case-Control Studies Odds Ratio biology.protein Humans SNP Family Female GABRA2 Genome-Wide Association Study |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:5082-5087 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0911109107 |
| Popis: | 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 α2 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. |
| Databáze: | OpenAIRE |
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