Study Report
Basic Info
Reference |
Wigg K, 200212042196
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Citation |
Wigg K., Zai G., Schachar R., Tannock R., Roberts W., Malone M., Kennedy J. L. and Barr C. L. (2002) "Attention deficit hyperactivity disorder and the gene for dopamine Beta-hydroxylase." Am J Psychiatry, 159(6): 1046-8.
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Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
117 families |
Predominant Ethnicity |
Canadian |
Population |
Canada |
Age Group |
Children/Adolescents
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Detail Info
Summary |
The authors investigated the linkage of the alleles and haplotypes of three polymorphisms at the DBH locus in 117 nuclear families with ADHD. No significant evidence was found for linkage of the TaqI alleles or haplotypes in the 117 families. However, the authors observed some evidence for biased transmission of the same allele of the TaqI polymorphism, as previously reported. These findings suggest that the gene for DBH should be investigated further. |
Total Sample |
117 families with a proband who had ADHD were involved in this study. The study group consisted of 92 families with both parents genotyped, 25 families with a single parent genotyped, and 33 affected siblings of the probands for a total of 150 children with ADHD. |
Sample Collection |
This protocol was approved by the Hospital for Sick Children's Research Ethics Board, and written informed consent was obtained for all participants. |
Diagnosis Description |
The assessment and characteristics of the subjects for this study have been described previously (Barr CL et al., 2000). |
Technique |
The intron 5 TaqI polymorphism was genotyped as previously described (Daly G et al., 1999). The second marker they used contains two polymorphisms - a (CA)n repeat and a 19-base-pair insertion/deletion - and was genotyped as previously described (Nahmias J et al., 1992). For the analysis the two polymorphisms were considered separately. The alleles for the (CA)n repeat were classified according to the designation of Wei J et al. [1997]. |
Analysis Method |
The transmission/disequilibrium test (TDT) statistic was calculated with the extended TDT program. Because the genotypes from affected siblings were used in the analysis, the test is more accurately described as a test for linkage as opposed to a test for association, and the term 'linkage' was used throughout the manuscript to describe the results. The TRANSMIT program was used to analyze the transmission of the haplotypes. Association between the markers was estimated with the EH program. |
Result Description |
The allele frequencies in the parental chromosomes were 0.480 for allele 1 (C) and 0.520 for allele 2 (T) for the TaqI polymorphism and 0.565 for the 19 base-pair insertion and 0.435 for the deletion. For the DBH (CA)n repeat the allele frequencies were 0.012, 0.070, 0.340, 0.571, and 0.007 for alleles A1 through A5, respectively. Significant association of the genotypes of the three polymorphisms (P=2E-12) was observed. The transmission/disequilibrium test results were not significant for the biased transmission of the alleles of the TaqI polymorphism; however, the biased transmission of allele 2 (transmitted 68 times compared with 52 times not transmitted) was also nonsignificant (TDT P=0.07). Biased transmission was not observed for either allele of the 19 base-pair polymorphism (TDT P=0.59) or for either of the two common alleles, A3 (TDT P=0.77) or A4 (TDT P=0.85), of the (CA)n repeat. No significant evidence for biased transmission of the haplotypes were found. |
Other variant reported by this study (count: 3)
Variant Name |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
DBH 5'-flanking (GT)n |
A3, A4 |
A4 |
TDT P-value=0.59
TDT P-value=0.59
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no significant evidence for biased transmission |
Non-significant
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DBH 5'-flanking ins/del |
insertion/deletion |
insertion |
TDT P-value=0.77 for allele A3, P-value=0.85 for allele A4
TDT P-value=0.77 for allele A3, P-value=0.85 for allele A4
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no significant evidence for biased transmission |
Non-significant
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DBH intron5 C/T TaqI |
C/T |
T |
TDT allele test P-value=0.07 (one-sided)
TDT allele test P-value=0.07 (one-sided)
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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 |
DBH |
TRANSMIT for haplotype transmission: smallest P=0.66. No sig......
TRANSMIT for haplotype transmission: smallest P=0.66. No significant evidence for biased transmission of the haplotypes and alleles were found.
More...
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Non-significant
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