Study Report
Basic Info
| Reference |
Barr CL, 2001(d)11425008
|
| Citation |
Barr C. L., Feng Y., Wigg K. G., Schachar R., Tannock R., Roberts W., Malone M. and Kennedy J. L. (2001) "5'-untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder." Am J Med Genet, 105(1): 84-90.
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| Study Design |
family-based |
| Study Type |
Candidate-gene association study |
| Sample Size |
82 families |
| Predominant Ethnicity |
Caucasian |
| Population |
Canada |
| Age Group |
Children/Adolescents
:
7-16 years
|
Detail Info
| Summary |
In this paper they extended the search for the molecular explanation for the observed association by testing three polymorphisms in the region 5' to the dopamine receptor D4 gene transcription start site for linkage to ADHD. They specifically targeted polymorphisms in the region 5' to the start site of transcription as DNA variants in this region could alter the transcription level of the gene and hence the phenotype. They did not observe significant evidence for biased transmission of any of the alleles at these three polymorphisms to ADHD probands using the transmission disequilibrium test. They conclude that these three polymorphisms are not related to the ADHD phenotype. |
| Total Sample |
For this study, they genotyped 82 families with an ADHD proband. Seventy-two of these families had both parental DNAs genotyped and the remainder of the families had DNA available and genotyped for a single parent. There were 15 affected siblings genotyped in the sample and included in the analyses. Haplotypes could be identified unambiguously in 63 of the families. The majority of families (96%) participating in this study described themselves as mixed European Caucasian descent with the most common ethnic groups being English, Scottish, Irish, German, French, Italian, Polish, and Dutch. Five families described themselves as being of mixed or non-Caucasian descent. |
| Sample Collection |
Subjects were referrals for clinical assessment of attention, behavior, and learning problems to one of two clinics at The Hospital for Sick Children. |
| Diagnosis Description |
For every case, diagnosis was based on information obtained from a semi-structured interview of the teacher [Teacher Telephone Interview-IV, TTI; R. Tannock, R. Schachar, unpublished data] and the parents [Parent Interview for Child Symptoms, PICS-IV; A. Schachar, Ickowicz, unpublished data]. This information was supplemented with standardized parent and teacher questionnaires: Conners Parent and Teacher Rating Scales-Revised [Conners, 1997] and the Ontario Child Health Survey Scales-Revised [Boyle et al., 1993]. |
| Technique |
DNA was extracted from blood lymphocytes using a standard high salt method [Miller et al., 1988]. The genotyping of the 120-bp duplication polymorphism was performed according to Seaman et al. [1999] with the following modifications. One hundred nanograms of genomic DNA was amplified in a total volume of 20 uL with the following primers at 2 ng/uL: D4upstrFor2 and D4upstrRev3; with 0.2 mM dNTPs, 5% dimethyl sulfoxide in standard polymerase chain reaction (PCR) buffer containing 1.5 mM MgCl2. |
| Analysis Method |
The transmission disequilibrium test (TDT) analysis was performed using the ETDT program [Sham and Curtis, 1995] for all markers and haplotypes. |
| Result Description |
They did not observe significant evidence for biased transmission of any of the alleles at these three polymorphisms to ADHD probands using the transmission disequilibrium test. They conclude that these three polymorphisms are not related to the ADHD phenotype. |
Other variant reported by this study (count: 3)
| Variant Name |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
| DRD4 promoter -616C/G |
C/G |
|
allelic P-value=0.154, X2=2.036
allelic P-value=0.154, X2=2.036
|
there was a trend for the transmission of allele C but this was also not significant |
Non-significant
|
| DRD4 promoter duplication 120bp |
1/2 repeat |
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allelic P-value=0.198, X2=1.658
allelic P-value=0.198, X2=1.658
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there was a trend for the transmission of the allele with 1 repeat, but this was not significant |
Non-significant
|
| DRD4 promoter -521C/T |
C/T |
|
allelic P-value=0.366, X2=0.818
allelic P-value=0.366, X2=0.818
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there was no evidence for biased transmission of the alleles |
Non-significant
|
Genes reported by this study (count: 1)
| Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
| DRD4 |
allele-wise TDT P-value>0.059, the result was not significan......
allele-wise TDT P-value>0.059, the result was not significant for any of the haplotypes of the 5' polymorphisms; the overall allele-wise TDT X2 and genotype-wise TDT X2 for the haplotypes of the 5' polymorphisms were not significant. Allele-wise TDT X2=3.903, d.f.=1, P-value=0.048 for haplotype composed of 2 repeats of the 120 bp polymorphism, allele 2 (T) of the FspI polymorphism, allele 1 (C) of the AvaII polymorphism and the 7-repeat allele of exon III (2-2-1-7) showed significant evidence for biased transmission; The overall genotype-wise TDT X2 for the haplotypes of the 5' polymorphisms and the exon III polymorphism was significant (TDT X2=68.282, 43 d.f., P=0.009) but the overall allele-wise TDT X2 was not
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Significant
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