title: Replication of genome wide association studies of alcohol dependence: support for association with variation in ADH1C.
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.
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic, Rochester, Minnesota, United States of America. biernacka.joanna@mayo.edu
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Biernacka
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Geske
authors.forename: Terry D
authors.initials: TD
authors.lastname: Schneekloth
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Tapp
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Lewis
authors.forename: Maureen S
authors.initials: MS
authors.lastname: Drews
authors.forename: Tracy
authors.initials: T
authors.lastname: L Pietrzak
authors.forename: Colin L
authors.initials: CL
authors.lastname: Colby
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Hall-Flavin
authors.forename: Larissa L
authors.initials: LL
authors.lastname: Loukianova
authors.forename: John A
authors.initials: JA
authors.lastname: Heit
authors.forename: David A
authors.initials: DA
authors.lastname: Mrazek
authors.forename: Victor M
authors.initials: VM
authors.lastname: Karpyak
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results
chemical_list: C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase