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	Bakker SC, 200515389755
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.
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

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		9R	allelic TDT P-value=0.32 allelic TDT P-value=0.32	no signs of a distorted transmissions of any of the single polymorphisms, or of single alleles	Non-significant
DRD4 exon3 VNTR		7R	allelic TDT P-value=0.50 allelic TDT P-value=0.50	no signs of a distorted transmissions of any of the single polymorphisms, or of single alleles	Non-significant
DRD4 intron1 (G)n			allelic TDT P-value=0.71 allelic TDT P-value=0.71	no signs of a distorted transmissions of any of the single polymorphisms, or of single alleles	Non-significant
SLC6A3 3'-UTR VNTR		10R	allelic TDT P-value=0.73 allelic TDT P-value=0.73	no signs of a distorted transmissions of any of the single polymorphisms, or of single alleles	Non-significant
SLC6A3 3'-flanking D5S2005			allelic TDT P-value=0.54 allelic TDT P-value=0.54	no signs of a distorted transmissions of any of the single polymorphisms, or of single alleles	Non-significant

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...	Non-significant
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...	Non-significant
DRD5	DRD5 did not contribute substantially to ADHD in the Dutch p...... DRD5 did not contribute substantially to ADHD in the Dutch population More...	Non-significant