Human Genetics

, Volume 132, Issue 10, pp 1141–1151

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

  • Manav Kapoor
  • Jen-Chyong Wang
  • Leah Wetherill
  • Nhung Le
  • Sarah Bertelsen
  • Anthony L. Hinrichs
  • John Budde
  • Arpana Agrawal
  • Kathleen Bucholz
  • Danielle Dick
  • Oscar Harari
  • Victor Hesselbrock
  • John Kramer
  • John I. NurnbergerJr
  • John Rice
  • Nancy Saccone
  • Marc Schuckit
  • Jay Tischfield
  • Bernice Porjesz
  • Howard J. Edenberg
  • Laura Bierut
  • Tatiana Foroud
  • Alison Goate
Original Investigation

DOI: 10.1007/s00439-013-1318-z

Cite this article as:
Kapoor, M., Wang, JC., Wetherill, L. et al. Hum Genet (2013) 132: 1141. doi:10.1007/s00439-013-1318-z

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.

Supplementary material

439_2013_1318_MOESM1_ESM.pdf (667 kb)
Supplementary material 1 (PDF 666 kb)
439_2013_1318_MOESM2_ESM.pdf (135 kb)
Supplementary material 2 (PDF 135 kb)
439_2013_1318_MOESM3_ESM.pdf (186 kb)
Supplementary material 3 (PDF 185 kb)
439_2013_1318_MOESM4_ESM.pdf (58 kb)
Supplementary material 4 (PDF 57 kb)
439_2013_1318_MOESM5_ESM.pdf (171 kb)
Supplementary material 5 (PDF 170 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Manav Kapoor
    • 1
  • Jen-Chyong Wang
    • 1
  • Leah Wetherill
    • 2
  • Nhung Le
    • 1
  • Sarah Bertelsen
    • 1
  • Anthony L. Hinrichs
    • 1
  • John Budde
    • 1
  • Arpana Agrawal
    • 1
  • Kathleen Bucholz
    • 1
  • Danielle Dick
    • 3
  • Oscar Harari
    • 1
  • Victor Hesselbrock
    • 4
  • John Kramer
    • 5
  • John I. NurnbergerJr
    • 2
  • John Rice
    • 1
  • Nancy Saccone
    • 9
  • Marc Schuckit
    • 6
  • Jay Tischfield
    • 7
  • Bernice Porjesz
    • 8
  • Howard J. Edenberg
    • 2
  • Laura Bierut
    • 1
  • Tatiana Foroud
    • 2
  • Alison Goate
    • 1
  1. 1.Department of Psychiatry, B8134Washington University School of MedicineSt. LouisUSA
  2. 2.Indiana University School of MedicineIndianapolisUSA
  3. 3.Virginia Commonwealth UniversityRichmondUSA
  4. 4.University of Connecticut Health CenterFarmingtonUSA
  5. 5.University of Iowa Carver College of MedicineIowaUSA
  6. 6.University of CaliforniaSan DiegoUSA
  7. 7.Rutgers UniversityPiscatawayUSA
  8. 8.SUNY Health Sciences CenterBrooklynUSA
  9. 9.Department of GeneticsWashington University School of MedicineSt. LouisUSA

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