Study Report
Basic Info
Reference |
Langley K, 200516082688
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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.
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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
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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 |
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polymorphism found through mutational analysis that has prev......
polymorphism found through mutational analysis that has previously been reported [Rubie et al., 2001]
More...
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Trend
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rs2652510 |
A/G |
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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...
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Non-significant
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rs2550956 |
T/C |
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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...
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Non-significant
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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 |
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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...
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no significant evidence for association was detected in the family-based and case-control analysis |
Non-significant
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SLC6A3 5'-flanking -3598A>G |
A/G |
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polymorphism found through mutational analysis |
Trend
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SLC6A3 5'-flanking -3911T>C |
T/C |
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polymorphism found through mutational analysis |
Trend
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SLC6A3 5'-flanking -4450C>G |
C/G |
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TDT P-value=0.94, Z-statistic=0.004
TDT P-value=0.94, Z-statistic=0.004
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not significantly associated with ADHD in family-based analysis |
Non-significant
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SLC6A3 5'-flanking -4532A>T |
A/T |
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polymorphism found through mutational analysis |
Trend
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
SLC6A3 |
no SNP showed significant association with ADHD; global tran......
no SNP showed significant association with ADHD; global transmit P-value=0.85 of 4-marker haplotype, yielded no evidence for association at a global level or for any specific single haplotype
More...
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Non-significant
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