A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks

Hum Genet. 2013 Oct;132(10):1141-51. doi: 10.1007/s00439-013-1318-z. Epub 2013 Jun 7.


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alcohol Drinking / genetics*
  • Alcoholism / genetics*
  • Chromosomes, Human, Pair 13 / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Gene-Environment Interaction
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Genetics, Population / methods
  • Genome, Human*
  • Genome-Wide Association Study*
  • Humans
  • LIM Domain Proteins / genetics
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Phosphoinositide Phospholipase C / genetics
  • Polymorphism, Single Nucleotide
  • Transcription Factors / genetics


  • DNA-Binding Proteins
  • LIM Domain Proteins
  • LMO1 protein, human
  • Transcription Factors
  • Phosphoinositide Phospholipase C
  • phospholipase C epsilon