Study Report
Basic Info
Reference |
Barr CL, 2000 (c)11032390
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Citation |
Barr C. L., Wigg K. G., Feng Y., Zai G., Malone M., Roberts W., Schachar R., Tannock R. and Kennedy J. L. (2000) "Attention-deficit hyperactivity disorder and the gene for the dopamine D5 receptor." Mol Psychiatry, 5(5): 548-51.
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Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
92 familie |
Predominant Ethnicity |
Caucasian |
Population |
Canada |
Age Group |
Children/Adolescents
:
aged 7-16 years
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Detail Info
Summary |
In this study they sought to replicate the association between (CA)n repeat of DRD5 and ADHD by testing for biased transmission of the alleles at this polymorphism in a sample of 92 families with an ADHD proband. No significant evidence was observed for biased transmission of the 148-bp allele, however biased transmission of two other alleles, the 136-bp allele and the 146-bp allele, were did observed. For these two alleles the bias was for these two alleles not to be transmitted to the ADHD children. The number of informative transmissions for these two alleles was small, therefore it would be premature to make any conclusions from the study concerning the role of DRD5 in ADHD. |
Total Sample |
92 families were genotyped, 80 consisting of a proband and both parental DNAs genotyped and 12 families with a proband with DNA available and genotyped for a single parent. There were 24 affected siblings genotyped in the sample for a total of 116 ADHD children. Of the cases that were used in this study, 57% of the children were of the combined subtype, 19% were of the hyperactive/impulsive subtype, and 24% were of the primarily inattentive subtype. |
Sample Collection |
This protocol was approved by The Hospital for Sick Children Research Ethics Board and informed written consent was obtained for all participants. |
Diagnosis Description |
Subjects in this study were between 7 and 16 years of age and met DSM-IV criteria for one of the three ADHD subtypes (inattentive, hyperactive-impulsive, combined). Subjects were excluded if they 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). Subjects were also excluded if they scored below 80 on both the Performance and Verbal Scales of the Wechsler Intelligence Scale for Children, 3rd edition. Subjects with comorbid oppositional defiant disorder, reading disabilities, or conduct disorder were not excluded from this study. Diagnosis was based on information obtained from a semi-structured interview of parents and teacher. Both interviews have established reliability and validity. This information was supplemented by evidence about behavior, development and medical history derived from standardized parent and teacher questionnaires; the Conners Parent and Teacher Rating Scales-Revised and the Ontario Child Health Survey Scales-Revised. Academic achievement in arithmetic, reading, and spelling were measured using the Wide Range Achievement Test-III. Oral and receptive language skills were tested with the Clinical Evaluation of Language Fundamentals, 3rd edition. Children were assessed using self-report for anxiety (Children's Manifest Anxiety Scale) and depression (Children's Depression Inventory). Children were free of medication 24 h before their assessment. |
Technique |
DNA was extracted directly from blood lymphocytes using a high salt extraction method. The (CA)n polymorphism located near the DRD5 gene was genotyped according to previous methods (Sherrington R et al., 1993). The fragments were separated on 1.3% agarose. Allele number 1 (A, asparagine) is identified as two bands of 480 bp and 171 bp. Allele number 2 (G, aspartic acid) could be detected as three bands of 387 bp, 93 bp, and 171 bp. |
Analysis Method |
Statistical analysis was performed using the ETDT program. |
Result Description |
Using the allele-wise test, no observe significant evidence for the biased transmission of the 148-bp allele was observed, however, there was a trend for the transmission of this allele to the ADHD children. Significant evidence for biased transmission of two alleles, the 136-bp allele and the 146-bp allele, were observed. For both of these alleles there were not many informative transmissions therefore the significance of the results should be interpreted with extreme caution as this could easily be the result of chance. |
Other variant reported by this study (count: 1)
Variant Name |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
DRD5 5'-flanking (CT/GT/GA)n |
134-156bp |
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TDT P-value=0.016 for allele 146 bp; TDT P-value=0.035 for a......
TDT P-value=0.016 for allele 146 bp; TDT P-value=0.035 for allele 136bp; TDT P-value=0.058 for allele 134bp; TDT P-value=0.281 for allele 148bp
More...
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no observe significant evidence for the biased transmission of the 148-bp allele was observed. Significant evidence for biased transmission of two alleles, the 136-bp allele and the 146-bp allele, were observed. |
Significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
DRD5 |
Significant evidence for biased transmission of two alleles,......
Significant evidence for biased transmission of two alleles, the 136-bp allele and the 146-bp allele, were observed.
More...
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Significant
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