Research article summary (published 30 Aug 2009):

Candidate genes involved in neural plasticity and the risk for attention-deficit hyperactivity disorder: a meta-analysis of 8 common variants.

Full Abstract

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is an important psychiatric condition in terms of its prevalence and impact on quality of life. It has one of the highest heritabilities found in psychiatric disorders. A number of association studies exploring several candidate genes in different populations around the world have been carried out. The objective of the present study was to carry out a meta-analysis for 8 common variants located in 5 top candidate genes for ADHD (BDNF, HTR1B, SLC6A2, SLC6A4 and SNAP25); these genes are known to be involved in synaptic transmission and plasticity. METHODS: We performed a search for published genetic association studies that analyzed the candidate polymorphisms in different populations, and we applied state-of-the-art meta-analytical procedures to obtain pooled odds ratios (ORs) and to evaluate potential basis of heterogeneity. We included 75 genetic association studies in these meta-analyses. RESULTS: A major part of the previously postulated associations were nonconsistent in the pooled odds ratios. We observed a weak significant association with a single nucleotide polymorphism (SNP) located in the 3' UTR region of the SNAP25 gene (rs3746544, T allele, OR 1.15, 95% confidence interval 1.01-1.31, p = 0.028, I(2) = 0%). In addition to the low coverage of genetic variability given by these variants, phenotypic heterogeneity between samples (ADHD subtypes, comorbidities) and genetic background may explain these differences. LIMITATIONS: Limitations of our study include the retrospective nature of our meta-analysis with the incorporation of study-level data from published articles. CONCLUSION: To our knowledge, the present study is the largest meta-analysis carried out for ADHD genetics; previously proposed cumulative associations with common polymorphisms in SLC6A4 and HTR1B genes were not supported. We identified a weak consistent association with a common SNP in the SNAP25 gene, a molecule that is known to be central for synaptic transmission and plasticity mechanisms.

Author information

Author/s: Forero, Diego A (DA); Arboleda, Gonzalo H (GH); Vasquez, Rafael (R); Arboleda, Humberto (H);

Affiliation: Neurosciences Research Group, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia. daforerog(-atsign-)unal.edu.co

Journal and publication information

Publication Type: Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't

Journal: Journal of psychiatry & neuroscience : JPN (J Psychiatry Neurosci), published in Canada. (Language: eng)

Reference: 2009-Sep; vol 34 (issue 5) : pp 361-6

Dates: Created 2009/09/01; Completed 2009/10/29;

PMID: 19721846, status: MEDLINE (last retrieval date: 10/29/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

3' Untranslated Regions Attention Deficit Disorder with Hyperactivity - genetics Brain-Derived Neurotrophic Factor - genetics Databases, Genetic Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study Genotype Humans

Neuronal Plasticity - genetics Norepinephrine Plasma Membrane Transport Proteins - genetics Odds Ratio Phenotype Polymorphism, Single Nucleotide Receptor, Serotonin, 5-HT1B - genetics Serotonin Plasma Membrane Transport Proteins - genetics Software Synaptosomal-Associated Protein 25 - genetics

Associated Chemicals: 3' Untranslated Regions (0) ; Brain-Derived Neurotrophic Factor (0) ; HTR1B protein, human (0) ; Norepinephrine Plasma Membrane Transport Proteins (0) ; Receptor, Serotonin, 5-HT1B (0) ; SLC6A2 protein, human (0) ; SLC6A4 protein, human (0) ; SNAP25 protein, human (0) ; Serotonin Plasma Membrane Transport Proteins (0) ; Synaptosomal-Associated Protein 25 (0)

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