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 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

doi:10.1073/pnas.0911109107

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 J. 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 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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374 Scopus citations

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 language	English
Pages (from-to)	5082-5087
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	107
Issue number	11
DOIs	https://doi.org/10.1073/pnas.0911109107
State	Published - 16 Mar 2010
Externally published	Yes

Keywords

Candidate genes
Genetics

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10.1073/pnas.0911109107

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Bierut, L. J., Agrawal, A., Bucholz, K. K., Doheny, K. F., Laurie, C., Pugh, E., Fisher, S., Fox, L., Howells, W., Bertelsen, S., Hinrichs, A. L., Almasy, L., Breslau, N., Culverhouse, R. C., Dick, D. M., Edenberg, H. J., Foroud, T., Grucza, R. A., Hatsukami, D., ... 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

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title = "A genome-wide association study of alcohol dependence",

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.",

keywords = "Candidate genes, Genetics",

author = "Bierut, {Laura J.} and Arpana Agrawal and Bucholz, {Kathleen K.} and Doheny, {Kimberly F.} and Cathy Laurie and Elizabeth Pugh and Sherri Fisher and Louis Fox and William Howells and Sarah Bertelsen and Hinrichs, {Anthony L.} and Laura Almasy and Naomi Breslau and Culverhouse, {Robert C.} and Dick, {Danielle M.} and Edenberg, {Howard J.} and Tatiana Foroud and Grucza, {Richard A.} and Dorothy Hatsukami and Victor Hesselbrock and Johnson, {Eric O.} and John Kramer and Krueger, {Robert F.} and Samuel Kuperman and Michael Lynskey and Karl Mann and Neuman, {Rosalind J.} and N{\"o}then, {Markus M.} and Nurnberger, {John I.} and Bernice Porjesz and Monika Ridinger and Saccone, {Nancy L.} and Saccone, {Scott F.} and Schuckit, {Marc A.} and Tischfield, {Jay A.} and Wang, {Jen C.} and Marcella Rietschel and Goate, {Alison M.} and Rice, {John P.}",

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doi = "10.1073/pnas.0911109107",

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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, HJ, 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, JI, 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

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T1 - A genome-wide association study of alcohol dependence

AU - Bierut, Laura J.

AU - Agrawal, Arpana

AU - Bucholz, Kathleen K.

AU - Doheny, Kimberly F.

AU - Laurie, Cathy

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 J.

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 I.

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.

PY - 2010/3/16

Y1 - 2010/3/16

N2 - 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.

AB - 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.

KW - Candidate genes

KW - Genetics

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U2 - 10.1073/pnas.0911109107

DO - 10.1073/pnas.0911109107

M3 - Article

C2 - 20202923

AN - SCOPUS:77950497675

SN - 0027-8424

VL - 107

SP - 5082

EP - 5087

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 11

ER -

A genome-wide association study of alcohol dependence

Abstract

Keywords

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