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	Langley K, 200516082688
Citation	Langley K., Turic D., Peirce T. R., Mills S., Van Den Bree M. B., Owen M. J., O'Donovan M. C. and Thapar A. (2005) "No support for association between the dopamine transporter (DAT1) gene and ADHD." Am J Med Genet B Neuropsychiatr Genet, 139B(1): 7-10.
Study Design	case-control and family-based
Study Type	Candidate-gene association study and Mutational study
Sample Size	263 trios and 287 controls
Predominant Ethnicity	Caucasian
Population	United Kingdom
Gender	238 male and 25 female probands
Age Group	Children/Adolescents : 6-16 years

Detail Info

Summary	They tested the DAT1 3'VNTR and three SNPs in the putative promoter region of DAT1 for association with ADHD in 263 parent-proband trios. Analyses of genotypes, alleles, and haplotypes were performed using family-based association methods. Case-control analysis of the VNTR in 263 cases and 287 controls was also conducted. In addition, they tested for association between the VNTR marker and stimulant medication response. Comparing allele 10 versus all other alleles combined, no significant association was found with ADHD, using FBAT analysis, and case-control analysis. No evidence of association with any of the SNPs in the promoter region was found. Haplotype analysis was also non-significant. Finally, no association was found between the DAT 1 VNTR and response to stimulant medication. They conclude that the 3' VNTR and three additional promoter variants in DAT1 do not appear to be associated with ADHD, or response to stimulant mediation in this sample.
Total Sample	All ADHD cases (n=263 (238 male, 25 female)) were of white British descent (including parents and grandparents), were aged between 6 and 16 years (mean 9 years 2 months, standard deviation 1 year 4 months) and met criteria for ICD-10 Hyperkinetic Disorder (HKD), DSM-IV ADHD, or DSM-III-R ADHD. In addition to this sample, a control group consisting of 287 white British healthy blood donors selected at random from the general practice registers in East Anglia, United Kingdom were available for case-control analysis.
Sample Collection	All ADHD cases were of white British descent (including parents and grandparents) and the control group selected at random from the general practice registers in East Anglia, United Kingdom.
Diagnosis Description	ICD-10 Hyperkinetic Disorder (HKD), DSM-IV ADHD, or DSM-III-R ADHD
Technique	Mutation analyses were performed using a WAVE DHPLC platform (Transgenomic); Relevant DNA fragments containing mutations were sequenced using Big Dye Terminator Cycle chemistry (Perkin Elmer Applied Biosystems, Cheshire, United Kingdom); The DAT1 VNTR was amplified as described by Holmes et al. [2000]. SNPs were genotyped by single nucleotide primer extension using a fluorescence polarization (FP) assay based upon AcycloPrime reagents (Perkin Elmer Life Science Products, Boston, MA); Analyses were performed using a LJL Biosystems Analyst platform.
Analysis Method	Family-based association analysis was performed for all SNPs using the transmission disequilibrium test (TDT) as implemented by the program Family-Based Association Test (FBAT); Haplotype analyses were performed using Transmit.
Result Description	Comparing allele 10 versus all other alleles combined, no significant association was found with ADHD, using FBAT analysis (chi2=0.1 (df 1), P=0.9, (odds ratio (OR)=1.0, 95% CI 0.8-1.2), and case-control analysis (chi2=0.12 (df 2), P=0.91). No evidence of association with any of the SNPs in the promoter region was found. Haplotype analysis was also non-significant (chi2=3.93, (df 9) global P=0.85).

SNPs reported by this study (count: 3)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs2652511	C/T			polymorphism found through mutational analysis that has prev...... polymorphism found through mutational analysis that has previously been reported [Rubie et al., 2001] More...	Trend
rs2652510	A/G		TDT P-value=0.83, Z-statistic=0.04	not significantly associated with ADHD in family-based analy...... not significantly associated with ADHD in family-based analysis More...	Non-significant
rs2550956	T/C		TDT P-value=0.55, Z-statistic=0.37	not significantly associated with ADHD in family-based analy...... not significantly associated with ADHD in family-based analysis More...	Non-significant

Other variant reported by this study (count: 5)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
SLC6A3 3'-UTR VNTR		10R	TDT P-value=0.61, Z-statistic=0.27 for 9R; TDT P-value=0.55,...... TDT P-value=0.61, Z-statistic=0.27 for 9R; TDT P-value=0.55, Z-statistic=0.39 for 10R in the family-based analysis; P-value=0.912, X²(1df)=0.12, OR=1.0 in the case-control analysis More...	no significant evidence for association was detected in the family-based and case-control analysis	Non-significant
SLC6A3 5'-flanking -3598A>G	A/G			polymorphism found through mutational analysis	Trend
SLC6A3 5'-flanking -3911T>C	T/C			polymorphism found through mutational analysis	Trend
SLC6A3 5'-flanking -4450C>G	C/G		TDT P-value=0.94, Z-statistic=0.004 TDT P-value=0.94, Z-statistic=0.004	not significantly associated with ADHD in family-based analysis	Non-significant
SLC6A3 5'-flanking -4532A>T	A/T			polymorphism found through mutational analysis	Trend

Genes reported by this study (count: 1)