Study Report

Basic Info
Reference |
Barr CL, 2000 (d)10686563
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Citation |
Barr C. L., Wigg K. G., Wu J., Zai C., Bloom S., Tannock R., Roberts W., Malone M., Schachar R. and Kennedy J. L. (2000) "Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder." Am J Med Genet, 96(1): 114-7.
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Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
100 families |
Predominant Ethnicity |
Caucasian |
Population |
Canada |
Age Group |
Children/Adolescents
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Detail Info
Summary |
In this study, they investigated the possibility of linkage of the dopamine D3 receptor gene in 100 small, nuclear families consisting of a proband with ADHD, their parents, and affected siblings. They examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test. No biased transmission of the alleles at either polymorphism or any haplotype were observed. The findings using this particular sample do not support the role of the dopamine D3 gene in ADHD. |
Total Sample |
100 families were used for this study , consisting of 84 families with a proband and both parental DNAs genotyped and 16 families with a proband with DNA available and genotyped for a single parent. Genotypes from 28 siblings of the probands who also met the criteria for ADHD were also used. Haplotypes could be determined unambiguously in 79 of these families-62 were probands with genotypes available from both parents, 16 of these were parent/child pairs, and there were 15 affected siblings. |
Sample Collection |
A sample of 100 families with an ADHD proband was tested in this study. This protocol was approved by The Hospital for Sick Children (Toronto, Ontario) Research Ethics Board and informed consent was obtained for all participants. |
Diagnosis Description |
Subjects were included if they met the following criteria for ADHD: (a) six symptoms of inattention and/or hyperactivity-impulsiveness either in the home or school setting as determined by clinical interview; (b) evidence of pervasiveness defined as a minimum of four symptoms in the non-criterion setting; (c) diagnostic decision in borderline cases included information from parent and teacher questionnaires; (d) not meeting exclusion criteria based on parent or teacher interview or on child assessment of anxiety or depression; (e) onset before 7 years of age. Subjects were excluded if they scored below 80 on both the Performance and Verbal Scales of the WISC-III, had evidence of neurological or chronic medical illness, bipolar affective disorder, psychotic symptoms, Tourette Syndrome, chronic multiple tics, or had a comorbid anxiety, depressive, or developmental disorder that could better account for the behaviors (as specified by DSM-IV). Children were free of medication for a minimum of 24 hr before their assessment. |
Technique |
DNA was extracted from blood lymphocytes using a high salt extraction method. The MscI (isoschizomer for BalI, New United Kingdom Biolabs) polymorphism located in the first exon of DRD3 was genotyped according to Lannfelt et al. [1992] and the MspI (New United Kingdom Biolabs) polymorphism in the fifth intron was genotyped as described [Griffon et al., 1996]. The restriction enzyme fragments were electrophoresed on 6% polyacrylamide mini gels (Novex) followed by silver staining to detect the alleles. |
Analysis Method |
Statistical analysis was performed using the ETDT program [Sham and Curtis, 1995]. Linkage disequilibrium between the two markers was estimated with the EH program [Ott, 1991]. |
Result Description |
Significant disequilibrium for the distribution of the genotypes (P=0.05) was observed. The TDT test was not significant for either allele of the MscI or MspI polymorphisms or for the haplotypes of these two polymorphisms. |

Other variant reported by this study (count: 2)
Variant Name |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
DRD3 exon1 Ser/Gly |
Ser/Gly |
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TDT P-value=0.322
TDT P-value=0.322
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no significant evidence for biased transmission |
Non-significant
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DRD3 intron5 MspI |
Absence/Presence |
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TDT P-value=0.769
TDT P-value=0.769
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no significant evidence for biased transmission |
Non-significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
DRD3 |
TDT of haplotypes: smallest P=0.317. No significant evidence......
TDT of haplotypes: smallest P=0.317. No significant evidence for either allele of the MscI or MspI polymorphisms or for the haplotypes of these two polymorphisms.
More...
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Non-significant
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