Genome-wide association studies of maximum number of drinks

Yue Pan, Xingguang Luo, Xuefeng Liu, Long Yang Wu, Qunyuan Zhang, Liang Wang, Weize Wang, Lingjun Zuo, Ke Sheng Wang

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Maximum number of drinks (MaxDrinks) defined as "Maximum number of alcoholic drinks consumed in a 24-h period" is an intermediate phenotype that is closely related to alcohol dependence (AD). Family, twin and adoption studies have shown that the heritability of MaxDrinks is approximately 0.5. We conducted the first genome-wide association (GWA) study and meta-analysis of MaxDrinks as a continuous phenotype. 1059 individuals were from the Collaborative Study on the Genetics of Alcoholism (COGA) sample and 1628 individuals were from the Study of Addiction - Genetics and Environment (SAGE) sample. Family sample with 3137 individuals was from the Australian twin-family study of alcohol use disorder (OZALC). Two population-based Caucasian samples (COGA and SAGE) with 1 million single-nucleotide polymorphisms (SNPs) were used for gene discovery and one family-based Caucasian sample was used for replication. Through meta-analysis we identified 162 SNPs associated with MaxDirnks (p<10-4). The most significant association with MaxDrinks was observed with SNP rs11128951 (p=4.27×10-8) near SGOL1 gene at 3p24.3. Furthermore, several SNPs (rs17144687 near DTWD2, rs12108602 near NDST4, and rs2128158 in KCNB2) showed significant associations with MaxDrinks (p<5×10-7) in the meta-analysis. Especially, 8 SNPs in DDC gene showed significant associations with MaxDrinks (p<5×10-7) in the SAGE sample. Several flanking SNPs in above genes/regions were confirmed in the OZALC family sample. In conclusions, we identified several genes/regions associated with MaxDrinks. These findings can improve the understanding about the pathogenesis of alcohol consumption phenotypes and alcohol-related disorders.

Original languageEnglish (US)
Pages (from-to)1717-1724
Number of pages8
JournalJournal of Psychiatric Research
Volume47
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • DDC
  • DTWD2
  • Genome-wide association
  • KCNB2
  • Maximum number of drinks
  • Meta-analysis
  • NDST4
  • SGOL1

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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