Meta-analysis of six genes (BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA) involved in neuroplasticity and the risk for alcohol dependence

Drug Alcohol Depend. 2015 Apr 1:149:259-63. doi: 10.1016/j.drugalcdep.2015.01.017. Epub 2015 Jan 24.

Abstract

Background: Alcohol-related problems have a large impact on human health, accounting for around 4% of deaths and 4.5% of disability-adjusted life-years around the world. Genetic factors could explain a significant fraction of the risk for alcohol dependence (AD). Recent meta-analyses have found significant pooled odds ratios (ORs) for variants in the ADH1B, ADH1C, DRD2 and HTR2A genes.

Methods: In the present study, we carried out a meta-analysis of common variants in 6 candidate genes involved in neurotransmission and neuroplasticity: BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA. We carried out a systematic search for published association studies that analyzed the genes of interest. Relevant articles were retrieved and demographic and genetic data were extracted. Pooled ORs were calculated using a random-effects model using the Meta-Analyst program. Dominant, recessive and allelic models were tested and analyses were also stratified by ethnicity.

Results: Forty two published studies were included in the current meta-analysis: BDNF-rs6265 (nine studies), DRD1-rs4532 (four studies), DRD3-rs6280 (eleven studies), DRD4-VNTR (seven studies), GRIN2B-rs1806201 (three studies) and MAOA-uVNTR (eight studies). We did not find significant pooled ORs for any of the six genes, under different models and stratifying for ethnicity.

Conclusions: In terms of the number of candidate genes included, this is one of the most comprehensive meta-analyses for genetics of AD. Pooled ORs did not support consistent associations with any of the six candidate genes tested. Future studies of novel genes of functional relevance and meta-analyses of quantitative endophenotypes could identify further susceptibility molecular factors for AD.

Keywords: Addiction; Alcoholism; Candidate genes; Neurogenetics.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alcoholism / genetics*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Male
  • Middle Aged
  • Models, Genetic
  • Monoamine Oxidase / genetics*
  • Neuronal Plasticity / genetics*
  • Receptors, Dopamine D1 / genetics*
  • Receptors, Dopamine D3 / genetics*
  • Receptors, Dopamine D4 / genetics*
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Synaptic Transmission / genetics
  • Young Adult

Substances

  • Brain-Derived Neurotrophic Factor
  • DRD1 protein, human
  • DRD3 protein, human
  • DRD4 protein, human
  • NR2B NMDA receptor
  • Receptors, Dopamine D1
  • Receptors, Dopamine D3
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Dopamine D4
  • Monoamine Oxidase
  • monoamine oxidase A, human