A genome-wide association study of alcohol dependence

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 Edenberg, Tatiana Foroud, Richard A. Grucza, Dorothy Hatsukami, Victor HesselbrockEric O. Johnson, John Kramer, Robert F. Krueger, Samuel Kuperman, Michael Lynskey, Karl Mann, Rosalind J. Neuman, Markus M. Nöthen, John 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

Research output: Contribution to journalArticle

334 Citations (Scopus)

Abstract

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 subjectwas 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 alcoholismphenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.

Original languageEnglish
Pages (from-to)5082-5087
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number11
DOIs
StatePublished - Mar 16 2010

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Genome-Wide Association Study
Alcoholism
Single Nucleotide Polymorphism
Drinking
Alcohols
GABA Receptors
Alcohol Drinking
African Americans
Substance-Related Disorders
Dissection
Cause of Death
Odds Ratio
Psychology
DNA
Genes

Keywords

  • Candidate genes
  • Genetics

ASJC Scopus subject areas

  • General

Cite this

Bierut, L. J., Agrawal, A., Bucholz, K. K., Doheny, K. F., Laurie, C., Pugh, E., ... Rice, J. P. (2010). A genome-wide association study of alcohol dependence. Proceedings of the National Academy of Sciences of the United States of America, 107(11), 5082-5087. https://doi.org/10.1073/pnas.0911109107

A genome-wide association study of alcohol dependence. / Bierut, Laura J.; Agrawal, Arpana; Bucholz, Kathleen K.; Doheny, Kimberly F.; Laurie, Cathy; Pugh, Elizabeth; Fisher, Sherri; Fox, Louis; Howells, William; Bertelsen, Sarah; Hinrichs, Anthony L.; Almasy, Laura; Breslau, Naomi; Culverhouse, Robert C.; Dick, Danielle M.; Edenberg, Howard; Foroud, Tatiana; Grucza, Richard A.; Hatsukami, Dorothy; Hesselbrock, Victor; Johnson, Eric O.; Kramer, John; Krueger, Robert F.; Kuperman, Samuel; Lynskey, Michael; Mann, Karl; Neuman, Rosalind J.; Nöthen, Markus M.; Nurnberger, John; Porjesz, Bernice; Ridinger, Monika; Saccone, Nancy L.; Saccone, Scott F.; Schuckit, Marc A.; Tischfield, Jay A.; Wang, Jen C.; Rietschel, Marcella; Goate, Alison M.; Rice, John P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 11, 16.03.2010, p. 5082-5087.

Research output: Contribution to journalArticle

Bierut, LJ, Agrawal, A, Bucholz, KK, Doheny, KF, Laurie, C, Pugh, E, Fisher, S, Fox, L, Howells, W, Bertelsen, S, Hinrichs, AL, Almasy, L, Breslau, N, Culverhouse, RC, Dick, DM, Edenberg, H, Foroud, T, Grucza, RA, Hatsukami, D, Hesselbrock, V, Johnson, EO, Kramer, J, Krueger, RF, Kuperman, S, Lynskey, M, Mann, K, Neuman, RJ, Nöthen, MM, Nurnberger, J, Porjesz, B, Ridinger, M, Saccone, NL, Saccone, SF, Schuckit, MA, Tischfield, JA, Wang, JC, Rietschel, M, Goate, AM & Rice, JP 2010, 'A genome-wide association study of alcohol dependence', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 11, pp. 5082-5087. https://doi.org/10.1073/pnas.0911109107
Bierut, Laura J. ; Agrawal, Arpana ; Bucholz, Kathleen K. ; Doheny, Kimberly F. ; Laurie, Cathy ; Pugh, Elizabeth ; Fisher, Sherri ; Fox, Louis ; Howells, William ; Bertelsen, Sarah ; Hinrichs, Anthony L. ; Almasy, Laura ; Breslau, Naomi ; Culverhouse, Robert C. ; Dick, Danielle M. ; Edenberg, Howard ; Foroud, Tatiana ; Grucza, Richard A. ; Hatsukami, Dorothy ; Hesselbrock, Victor ; Johnson, Eric O. ; Kramer, John ; Krueger, Robert F. ; Kuperman, Samuel ; Lynskey, Michael ; Mann, Karl ; Neuman, Rosalind J. ; Nöthen, Markus M. ; Nurnberger, John ; Porjesz, Bernice ; Ridinger, Monika ; Saccone, Nancy L. ; Saccone, Scott F. ; Schuckit, Marc A. ; Tischfield, Jay A. ; Wang, Jen C. ; Rietschel, Marcella ; Goate, Alison M. ; Rice, John P. / A genome-wide association study of alcohol dependence. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 11. pp. 5082-5087.
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AU - Agrawal, Arpana

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AU - Doheny, Kimberly F.

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AU - Pugh, Elizabeth

AU - Fisher, Sherri

AU - Fox, Louis

AU - Howells, William

AU - Bertelsen, Sarah

AU - Hinrichs, Anthony L.

AU - Almasy, Laura

AU - Breslau, Naomi

AU - Culverhouse, Robert C.

AU - Dick, Danielle M.

AU - Edenberg, Howard

AU - Foroud, Tatiana

AU - Grucza, Richard A.

AU - Hatsukami, Dorothy

AU - Hesselbrock, Victor

AU - Johnson, Eric O.

AU - Kramer, John

AU - Krueger, Robert F.

AU - Kuperman, Samuel

AU - Lynskey, Michael

AU - Mann, Karl

AU - Neuman, Rosalind J.

AU - Nöthen, Markus M.

AU - Nurnberger, John

AU - Porjesz, Bernice

AU - Ridinger, Monika

AU - Saccone, Nancy L.

AU - Saccone, Scott F.

AU - Schuckit, Marc A.

AU - Tischfield, Jay A.

AU - Wang, Jen C.

AU - Rietschel, Marcella

AU - Goate, Alison M.

AU - Rice, John P.

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