Study Report
Basic Info
Reference |
Bakker SC, 200515389755
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Citation |
Bakker S. C., van der Meulen E. M., Oteman N., Schelleman H., Pearson P. L., Buitelaar J. K. and Sinke R. J. (2005) "DAT1, DRD4, and DRD5 polymorphisms are not associated with ADHD in Dutch families." Am J Med Genet B Neuropsychiatr Genet, 132B(1): 50-2.
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Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
236 Dutch children from 144 families |
Predominant Ethnicity |
Caucasian |
Population |
the Netherlands |
Age Group |
Children/Adolescents
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Detail Info
Summary |
In a family-based sample of 236 Dutch children with ADHD, they have investigated the previously described variable number of tandem repeat (VNTR) polymorphisms and two additional microsatellites at the DAT1 and DRD4 loci. DRD5 was investigated using the microsatellite that was previously found to be associated. Transmission disequilibrium tests (TDTs) did not show preferential transmission of alleles or two-marker haplotypes to affected offspring. These data suggest that DAT1, DRD4, and DRD5 do not contribute substantially to ADHD in the Dutch population. |
Total Sample |
The sample comprises of 236 Dutch children from 144 families. This sample was extended with 38 families with only 1 affected child, diagnosed using the same criteria. In five families, no DNA from the father was available. |
Sample Collection |
Most children (n=198) were part of a previously described sample of sib pair families [Bakker et al., 2003]. |
Diagnosis Description |
Children were only included if they had ADHD of the inattentive, hyperactive, or combined subtype, according to DSM-IV criteria. Children with autism spectrum disorders were excluded. |
Technique |
DNA was isolated as described [Bakker et al., 2003]. The VNTR polymorphisms in the DAT1 and DRD4 genes were amplified using previously described PCR primers [Van Tol et al., 1992; Cook et al., 1995]. PCR reactions were performed on a ABI 9600 GeneAmp PCR system (Applied Biosystems). Detailed description could be found in the original publication. |
Analysis Method |
Hardy-Weinberg equilibrium (HWE) was investigated using the GENEPOP program for multi-allelic markers [Raymond and Rousset, 1995]. Likelihood ratios for transmissions of marker alleles and haplotypes from parents to affected offspring, as well as linkage disequilibrium (LD) between markers, were calculated using the TDTPHASE program [Dudbridge, 2003]. This estimates missing haplotypes using the expectation maximization (EM) algorithm, and uses unconditional logistic regression on the full likelihood of parents and offspring. Only alleles and haplotypes with frequencies higher than 0.05 were taken into account. P values were not corrected for multiple testing. |
Result Description |
Transmission disequilibrium tests (TDTs) did not show preferential transmission of alleles or two-marker haplotypes to affected offspring. These data suggest that DAT1, DRD4, and DRD5 do not contribute substantially to ADHD in the Dutch population. |
Other variant reported by this study (count: 5)
Variant Name |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
DRD5 5'-flanking (CT/GT/GA)n |
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9R |
allelic TDT P-value=0.32
allelic TDT P-value=0.32
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no signs of a distorted transmissions of any of the single polymorphisms, or of single alleles |
Non-significant
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DRD4 exon3 VNTR |
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7R |
allelic TDT P-value=0.50
allelic TDT P-value=0.50
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no signs of a distorted transmissions of any of the single polymorphisms, or of single alleles |
Non-significant
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DRD4 intron1 (G)n |
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allelic TDT P-value=0.71
allelic TDT P-value=0.71
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no signs of a distorted transmissions of any of the single polymorphisms, or of single alleles |
Non-significant
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SLC6A3 3'-UTR VNTR |
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10R |
allelic TDT P-value=0.73
allelic TDT P-value=0.73
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no signs of a distorted transmissions of any of the single polymorphisms, or of single alleles |
Non-significant
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SLC6A3 3'-flanking D5S2005 |
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allelic TDT P-value=0.54
allelic TDT P-value=0.54
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no signs of a distorted transmissions of any of the single polymorphisms, or of single alleles |
Non-significant
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Genes reported by this study (count: 3)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
DRD4 |
haplotype DRD4, TDT P-value=0.65; DRD4 did not contribute su......
haplotype DRD4, TDT P-value=0.65; DRD4 did not contribute substantially to ADHD in the Dutch population
More...
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Non-significant
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SLC6A3 |
haplotype SLC6A3, TDT P-value=0.21; SLC6A3 did not contribut......
haplotype SLC6A3, TDT P-value=0.21; SLC6A3 did not contribute substantially to ADHD in the Dutch population
More...
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Non-significant
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DRD5 |
DRD5 did not contribute substantially to ADHD in the Dutch p......
DRD5 did not contribute substantially to ADHD in the Dutch population
More...
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Non-significant
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