ADHDgene Database

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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

Study Report

Basic Info

Reference	Brookes KJ, 2005 (b)16082702
Citation	Brookes K. J., Knight J., Xu X. and Asherson P. (2005) "DNA pooling analysis of ADHD and genes regulating vesicle release of neurotransmitters." Am J Med Genet B Neuropsychiatr Genet, 139B(1): 33-7.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	180 probands and their parents, 180 controls
Predominant Ethnicity	Caucasian
Population	United Kingdom
Gender	96% male probands, 90 male and 90 female controls
Age Group	Children/Adolescents

Detail Info

Summary	They therefore investigated other genes that produce proteins that interact with SNAP-25 in the mechanism of vesicular release of neurotransmitters at the synapse. A total of 106 SNPs were screened for minor allele frequency greater than 5% and 61 SNPs selected for analysis in DNA pools made up from an ADHD clinical sample of DSM-IV combined type probands (n=180) and a control sample of 90 males and 90 females. Initial screening identified several SNPs that showed allele frequency differences of 5% or more. One SNP in the synaptophysin gene showed suggestive evidence of association following case-control and TDT analysis and warrants further investigation.
Total Sample	The sample analyzed here consisted of 180 probands. DNA was available from both parents for 121 probands and from only the mother for 64 probands. Ninety-six percent of the probands were male. A control sample was generated from ethnically matched individuals taking part in a population twin sample [Trouton et al., 2002]. This comprised 90 unrelated females and 90 unrelated males selected for low ADHD symptoms scores (lower 20%) using a composite index of ADHD symptoms.
Sample Collection	The clinical ADHD samples were ascertained from Child and Adolescent clinics in London and the South East of United Kingdom. A control sample was generated from ethnically matched individuals taking part in a population twin sample [Trouton et al., 2002].
Diagnosis Description	All probands had a research diagnosis of ADHD combined subtype following the DSM-IV criteria [APA, 1994].
Technique	The concentration of each DNA sample was measured using the PicoGreen dsDNA quantitation reagent (Cambridge Biosciences) in a Fluorimeter (Thermo Life Sciences). Each genotype assay was analyzed in triplicate on each pool using the SNaPshot method (ABI, Foster City).
Analysis Method	They adopted a meta-regression method (MRM) for the analysis of multiple pools [Xu et al., 2005]. SNPs that obtained an MRM significance level <0.1 were individually genotyped in the case and control samples, plus parents and siblings of the probands. TDT analysis was performed using unphased [Dudbridge, 2003].
Result Description	Initial screening identified several SNPs that showed allele frequency differences of 5% or more. One SNP in the synaptophysin gene showed suggestive evidence of association following case-control and TDT analysis and warrants further investigation.

SNPs reported by this study (count: 5)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs316987			MRM P-value=0.29, Case-control P-value=0.91, TDT P-value=0.3	was not significant in both TDT analysis and case-control an...... was not significant in both TDT analysis and case-control analysis More...	Non-significant
rs1245769			MRM P-value=0.09, Case-control P-value=0.23, TDT P-value=0.73	was not significant in both TDT analysis and case-control an...... was not significant in both TDT analysis and case-control analysis More...	Non-significant
rs2293945			MRM P-value=0.03, Case-control P-value=0.09, TDT P-value=0.005	remained significant following case-control and TDT analysis...... remained significant following case-control and TDT analysis of the individually genotyped data More...	Significant
rs1569061			MRM P-value=0.75, Case-control P-value=0.24, TDT P-value=0.04	was not significant in case-control analysis, but showed nom...... was not significant in case-control analysis, but showed nominal significance in TDT analysis More...	Significant
rs363225			MRM P-value=0.49, Case-control P-value=0.31, TDT P-value=0.4	was not significant in both TDT analysis and case-control an...... was not significant in both TDT analysis and case-control analysis More...	Non-significant

Genes reported by this study (count: 5)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
SLC18A2	no SNP showed evidence of association no SNP showed evidence of association	Non-significant
SYP	1 SNP remained significant following case-control and TDT an...... 1 SNP remained significant following case-control and TDT analysis of the individually genotyped data More...	Significant
VAMP2	no SNP showed evidence of association no SNP showed evidence of association	Non-significant
STX1A	1 SNP showed nominal significance in TDT analysis 1 SNP showed nominal significance in TDT analysis	Significant
SYT1	no SNP showed evidence of association no SNP showed evidence of association	Non-significant