title: Meta-analysis of six genes (BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA) involved in neuroplasticity and the risk for alcohol dependence.
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.
authors: Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia. Electronic address: diego.forero@uan.edu.co.
authors: Diego A
authors: DA
authors: Forero
authors: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors: Sandra
authors: S
authors: López-León
authors: Laboratory of Genomic Diversity, Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors: Hyoung Doo
authors: HD
authors: Shin
authors: Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Republic of Korea.
authors: Byung Lae
authors: BL
authors: Park
authors: Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Dai-Jin
authors: DJ
authors: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D008995:Monoamine Oxidase / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C583260:DRD1 protein, human; C493593:DRD3 protein, human; C493599:DRD4 protein, human; C121001:NR2B NMDA receptor; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D016194:Receptors, N-Methyl-D-Aspartate; D050638:Receptors, Dopamine D4; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human
keywords: Addiction; Alcoholism; Candidate genes; Neurogenetics