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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	Wigg K, 200212042196
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.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	117 families
Predominant Ethnicity	Canadian
Population	Canada
Age Group	Children/Adolescents

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	no significant evidence for biased transmission	Non-significant
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	no significant evidence for biased transmission	Non-significant
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)	no significant evidence for biased transmission	Non-significant

Genes reported by this study (count: 1)