ADHDgene Database

Hot Results

Quick Search

Keyword:
Type:

Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Meta-analysis Report

Basic Info

Reference	Li D, 200616774975
Citation	Li D., Sham P. C., Owen M. J. and He L. (2006) "Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD)." Hum Mol Genet, 15(14): 2276-84.
Study Type	Candidate association study
Summary	Molecular genetic investigations of attention deficit hyperactivity disorder (ADHD) have found associations with a variable number of tandem repeat (VNTR) situated in the 3'-untranslated region of dopamine transporter gene (DAT1), a VNTR in exon 3 of dopamine receptor 4 gene (DRD4 ) and a microsatellite polymorphism located at 18.5 kb from the 5' end of dopamine receptor 5 gene (DRD5). A number of independent studies have attempted to replicate these findings but the results have been mixed, possibly reflecting inadequate statistical power and the use of different populations and methodologies. In an attempt to clarify this inconsistency, they have combined all the published studies of European and Asian populations up to October 2005 in a meta-analysis to give a comprehensive picture of the role of the three dopamine-related genes using multiple research methods and models. The DRD4 7-repeat and 5-repeat alleles as well as the DRD5 148-bp allele confer increased risk of ADHD, whereas the DRD4 4-repeat and DRD5 136-bp alleles have protective effects. In contrast, they found no compelling evidence for association with the 480-bp allele of DAT. No significant publication bias was detected in current studies. In conclusion, there is a statistically significant association between ADHD and dopamine system genes, especially DRD4 and DRD5.

Detail Info

Samples	The publications included in the analysis were selected from PubMed and from www.cnki.net/index.htm with keywords 'attention deficit hyperactivity disorder', 'ADHD', 'dopamine transporter', 'dopamine 4 receptor', 'dopamine 5 receptor', 'association' and the specific names and abbreviations of each gene (e.g. 'dopamine receptor 4'and 'DRD4'). All references cited in these studies and in published reviews were examined in order to identify additional works not indexed by MEDLINE. The analyzed data cover all English and Chinese publications from April 1995 to October 2005. As a result, 26, 38 and 9 studies were included for the DAT1, DRD4 and DRD5 genes, respectively. These studies included 2576 cases, 3453 controls and 6592 parent-offspring trios.
Statistic Method	Data from the case-control, HRR and HHRR studies were summarized by two-by-two tables (meta-analysis was conducted based on allele data, i.e. HHRR methodology, for studies that originally used HRR or HHRR for analysis) and TDT studies were summarized by two-by-one tables. The two types of studies were statistically combined by the method used by Lohmueller et al., Cho et al. and Li et al. to join case-control and family-based studies into a single meta-analysis. From each table, a log-odds ratio and its sampling variance were calculated. Cochran¡¯s X²-based Q statistic test was performed in order to assess possible heterogeneity of OR between the individual studies. Heterogeneity Q tests were also performed for differences in OR between design types (case-control versus family-based), and between sample ethnicities (European versus Asian). A test for funnel plot asymmetry, described by Egger et al., was used to assess evidence for publication bias. ORs were pooled using the method of DerSimonian and Laird and 95% CIs were constructed using Woolf's method. The significance of the overall OR was determined by the Z-test. The analysis was conducted by Comprehensive Meta Analysis software (Version 1.0.23, BIOSTAT, Englewood, NJ, USA).
Basic Result	The DRD4 7-repeat (OR=1.34, 95% CI 1.23-1.45, P=210^-12 and 5-repeat (OR=1.68, 95% CI 1.17-2.41, P=0.005) alleles as well as the DRD5 148-bp allele (OR=1.34, 95% CI 1.21-1.49, P=810^-8) confer increased risk of ADHD, whereas the DRD4 4-repeat (OR=0.90, 95% CI 0.84-0.97, P=0.004) and DRD5 136-bp (OR=0.57, 95% CI 0.34-0.96, P=0.022) alleles have protective effects. In contrast, they found no compelling evidence for association with the 480-bp allele of DAT (OR=1.04, 95% CI 0.98-1.11, P=0.20). No significant publication bias was detected in current studies.

Genes reported by this study: 3

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
DRD5	DRD5 148-bp showed a significant association, there is a sta...... DRD5 148-bp showed a significant association, there is a statistically significant association between ADHD and DRD5 More...	Significant
DRD4	DRD4 4-repeat, 5-repeat, 7-repeat showed significant associa...... DRD4 4-repeat, 5-repeat, 7-repeat showed significant associations, there is a statistically significant association between ADHD and DRD4 More...	Significant
SLC6A3	SLC6A3 520-bp risk allele (P-value=0.05) showed a weak signi...... SLC6A3 520-bp risk allele (P-value=0.05) showed a weak significant association More...	Significant