A large-scale meta-analysis of the association between the ANKK1/DRD2 Taq1A polymorphism and alcohol dependence

Hum Genet. 2013 Mar;132(3):347-58. doi: 10.1007/s00439-012-1251-6. Epub 2012 Dec 1.

Abstract

Alcohol dependence (AD) is a common neuropsychiatric disorder with high heritability. A number of studies have analyzed the association between the Taq1A polymorphism (located in the gene cluster ANKK1/DRD2) and AD. In the present study, we conducted a large-scale meta-analysis to confirm the association between the Taq1A polymorphism and the risk for AD in over 18,000 subjects included in 61 case-control studies that were published up to August 2012. Our meta-analysis demonstrated both allelic and genotypic association between the Taq1A polymorphism and AD susceptibility [allelic: P(Z) = 1.1 × 10(-5), OR = 1.19; genotypic: P(Z) = 3.2 × 10(-5), OR = 1.24]. The association remained significant after adjustment for publication bias using the trim and fill method. Sensitivity analysis showed that the effect size of the Taq1A polymorphism on AD risk was moderate and not influenced by any individual study. The pooled odds ratio from published studies decreased with the year of publication, but stabilized after the year 2001. Subgroup analysis indicated that publication bias could be influenced by racial ancestry. In summary, this large-scale meta-analysis confirmed the association between the Taq1A polymorphism and AD. Future studies are required to investigate the functional significance of the ANKK1/DRD2 Taq1A polymorphism in AD.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Alcoholism / ethnology
  • Alcoholism / genetics*
  • Asian People / genetics
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Protein Serine-Threonine Kinases / genetics*
  • Publication Bias
  • Receptors, Dopamine D2 / genetics*
  • Sensitivity and Specificity
  • Sex Factors
  • Taq Polymerase / genetics*
  • White People / genetics

Substances

  • Receptors, Dopamine D2
  • ANKK1 protein, human
  • Protein Serine-Threonine Kinases
  • Taq Polymerase