title: A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.
abstract: Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case-control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1 × 10(-6)) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 × 10(-7)), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 × 10(-7)) and PLCL1 genes (p = 4.1 × 10(-6)) with maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p ≤ 10(-4)) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 × 10(-3), 3 × 10(-6)), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.
authors.affiliation: Department of Psychiatry, B8134, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO, 63110, USA.
authors.forename: Manav
authors.initials: M
authors.lastname: Kapoor
authors.forename: Jen-Chyong
authors.initials: JC
authors.lastname: Wang
authors.forename: Leah
authors.initials: L
authors.lastname: Wetherill
authors.forename: Nhung
authors.initials: N
authors.lastname: Le
authors.forename: Sarah
authors.initials: S
authors.lastname: Bertelsen
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Hinrichs
authors.forename: John
authors.initials: J
authors.lastname: Budde
authors.forename: Arpana
authors.initials: A
authors.lastname: Agrawal
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bucholz
authors.forename: Danielle
authors.initials: D
authors.lastname: Dick
authors.forename: Oscar
authors.initials: O
authors.lastname: Harari
authors.forename: Victor
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: John
authors.initials: J
authors.lastname: Kramer
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: John
authors.initials: J
authors.lastname: Rice
authors.forename: Nancy
authors.initials: N
authors.lastname: Saccone
authors.forename: Marc
authors.initials: M
authors.lastname: Schuckit
authors.forename: Jay
authors.initials: J
authors.lastname: Tischfield
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Laura
authors.initials: L
authors.lastname: Bierut
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population / Q000379:methods; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D054801:Phosphoinositide Phospholipase C / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C065072:LMO1 protein, human; D014157:Transcription Factors; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon