ADHDgene Database

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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	Todd RD, 200516178930
Citation	Todd R. D., Huang H., Smalley S. L., Nelson S. F., Willcutt E. G., Pennington B. F., Smith S. D., Faraone S. V. and Neuman R. J. (2005) "Collaborative analysis of DRD4 and DAT genotypes in population-defined ADHD subtypes." J Child Psychol Psychiatry, 46(10): 1067-73.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	2,090 offspring and both biological parents
Predominant Ethnicity	Caucasian
Population	USA
Gender	no ADHD DSM-IV diagnosis: 56.1% male, 43.9% female; inattentive subtype: 75.9% male, 24.1% female; hyperactive subtype: 74.1% male, 25.9% female; combined subtype: 79.9% male, 20.1% female
Age Group	Children/Adolescents : average age: 9-14 years

Detail Info

Summary	Three studies which had previously reported no associations between polymorphisms of the DRD4 and DAT genes and DSM-IV defined ADHD were reanalyzed using population-based and DSM-IV defined ADHD subtypes. Across studies no significant associations were found for either DRD4 or DAT polymorphisms using DSM-IV ADHD subtypes. In contrast, a significant association was found between the combined data set for the 440 base pair 3' DAT VNTR polymorphism and population-defined severe combined ADHD. A marginally significant association was also found between the 7 repeat DRD4 allele and population-defined severe combined ADHD.
Total Sample	There were a total of 2,090 individual offspring included in the analyses. Of these, 1,352 had no ADHD DSM-IV diagnosis, 316 were primarily inattentive subtype, 54 were primarily hyperactive/ impulsive subtype, and 368 were combined subtype. Fifty-four individuals had ambiguous assignments to the population-based subtypes and were removed from further analyses.
Sample Collection	These three data sets (from the University of Colorado at Boulder (UCB), from the University of California at Los Angeles (UCLA), and from Washington University School of Medicine, St. Louis (WUMS)) contained complete clinical and genotypic information on 2,090 offspring and genotypic information on both biological parents.
Diagnosis Description	Details of the design, sampling and diagnostic assessments used for each study can be found in Smalley et al. (2000:UCLA), Todd et al. (2003a:WUSM) and Willcutt et al. (2005: UCB).
Technique	For all three studies similar genotyping methods were used based on the primers originally reported by Cook et al. (1995) for the 3' VNTR of the dopamine transporter gene (DAT) and those of LaHoste et al. (1996) for the exon 3 48-base pair repeat of the human dopamine DRD4 receptor gene. Samples were not exchanged between laboratories but the allele frequency distributions for both polymorphisms were nearly identical for three samples.
Analysis Method	Genetic associations were estimated using the program Transmit (Version 2.5.4) (Clayton, 1999).
Result Description	Across studies no significant associations were found for either DRD4 or DAT polymorphisms using DSM-IV ADHD subtypes. In contrast, a significant association was found between the combined data set for the 440 base pair 3' DAT VNTR polymorphism and population-defined severe combined ADHD (OR=1.25, p=0.01). A marginally significant association was also found between the 7 repeat DRD4 allele and population-defined severe combined ADHD.

Other variant reported by this study (count: 2)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
SLC6A3 3'-UTR VNTR		440bp allele	TRANSMIT P-value=0.09 for 440bp allele; TRANSMIT P-value=0.1...... TRANSMIT P-value=0.09 for 440bp allele; TRANSMIT P-value=0.1 for 480bp allele More...	there was a trend for significant under-transmission of the 440 and 480 base pair allele for the DSM-IV combined ADHD subtype in the total sample	Non-significant
DRD4 exon3 VNTR	4R/7R		data not shown in the publication data not shown in the publication	no significant association was found with DSM-IV defined ADHD or ADHD subtypes	Non-significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
SLC6A3	no significant associations were found for SLC6A3 polymorphi...... no significant associations were found for SLC6A3 polymorphisms using DSM-IV ADHD subtypes More...	Non-significant
DRD4	no significant associations were found for DRD4 polymorphism...... no significant associations were found for DRD4 polymorphisms using DSM-IV ADHD subtypes More...	Non-significant