Replication of Genome Wide Association Studies of Alcohol Dependence: Support for Association with Variation in ADH1C

Joanna M Biernacka, Jennifer R. Geske, Terry D. Schneekloth, Mark A Frye, Julie M Cunningham, Doo Sup Choi, Courtney L. Tapp, Bradley R. Lewis, Maureen S. Drews, Tracy L.Pietrzak, Colin L. Colby, Daniel K. Hall-Flavin, Larissa L. Loukianova, John A. Heit, David A. Mrazek, Victor M Karpyak

Research output: Contribution to journalArticle

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Abstract

Genome-wide association studies (GWAS) have revealed many single nucleotide polymorphisms (SNPs) associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017). Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI) = 0.80 (0.66, 0.95); women: OR (95%CI) = 0.83 (0.66, 1.03)). We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081), and independently in the alcohol-dependent cases (p = 0.046). Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.

Original languageEnglish (US)
Article numbere58798
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 13 2013

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Genome-Wide Association Study
alcohol abuse
single nucleotide polymorphism
Alcoholism
Single Nucleotide Polymorphism
Genes
Alcohols
Polymorphism
alcohols
Nucleotides
gender
Alcohol Drinking
genome-wide association study
genes
Alleles
genetic polymorphism
alleles
Phenotype
phenotype
Population

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Replication of Genome Wide Association Studies of Alcohol Dependence : Support for Association with Variation in ADH1C. / Biernacka, Joanna M; Geske, Jennifer R.; Schneekloth, Terry D.; Frye, Mark A; Cunningham, Julie M; Choi, Doo Sup; Tapp, Courtney L.; Lewis, Bradley R.; Drews, Maureen S.; L.Pietrzak, Tracy; Colby, Colin L.; Hall-Flavin, Daniel K.; Loukianova, Larissa L.; Heit, John A.; Mrazek, David A.; Karpyak, Victor M.

In: PLoS One, Vol. 8, No. 3, e58798, 13.03.2013.

Research output: Contribution to journalArticle

Biernacka, JM, Geske, JR, Schneekloth, TD, Frye, MA, Cunningham, JM, Choi, DS, Tapp, CL, Lewis, BR, Drews, MS, L.Pietrzak, T, Colby, CL, Hall-Flavin, DK, Loukianova, LL, Heit, JA, Mrazek, DA & Karpyak, VM 2013, 'Replication of Genome Wide Association Studies of Alcohol Dependence: Support for Association with Variation in ADH1C', PLoS One, vol. 8, no. 3, e58798. https://doi.org/10.1371/journal.pone.0058798
Biernacka, Joanna M ; Geske, Jennifer R. ; Schneekloth, Terry D. ; Frye, Mark A ; Cunningham, Julie M ; Choi, Doo Sup ; Tapp, Courtney L. ; Lewis, Bradley R. ; Drews, Maureen S. ; L.Pietrzak, Tracy ; Colby, Colin L. ; Hall-Flavin, Daniel K. ; Loukianova, Larissa L. ; Heit, John A. ; Mrazek, David A. ; Karpyak, Victor M. / Replication of Genome Wide Association Studies of Alcohol Dependence : Support for Association with Variation in ADH1C. In: PLoS One. 2013 ; Vol. 8, No. 3.
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abstract = "Genome-wide association studies (GWAS) have revealed many single nucleotide polymorphisms (SNPs) associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017). Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95{\%}CI) = 0.80 (0.66, 0.95); women: OR (95{\%}CI) = 0.83 (0.66, 1.03)). We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081), and independently in the alcohol-dependent cases (p = 0.046). Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.",
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