ADHDgene Database

Hot Results

Quick Search

Keyword:
Type:

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	Swanson JM, 19989491811
Citation	Swanson J. M., Sunohara G. A., Kennedy J. L., Regino R., Fineberg E., Wigal T., Lerner M., Williams L., LaHoste G. J. and Wigal S. (1998) "Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach." Mol Psychiatry, 3(1): 38-41.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	105 probands from 52 families
Predominant Ethnicity
Population	USA
Age Group	Children/Adolescents : aged 7-12 years

Detail Info

Summary	Previously in this journal, they reported an association of the dopamine D4 receptor gene (DRD4) and attention deficit hyperactivity disorder (ADHD). In a population-association (case-control) study of 39 children with a refined phenotype of ADHD and 39 ethnically matched controls, they observed an increased percentage of the 7 repeat allele (29% vs 12%) and the 7+ genotype (49% vs 21%) in the ADHD group compared to the control group. In a replication and an extension of initial study, they recruited another sample of ADHD subjects and found percentages of the 7 repeat allele (28%) and the 7+ genotype (48%) consistent with our previous findings. They used a family-based approach to evaluate a predicted association of DRD4 and ADHD based on a test of allele transmission focused on the 7 repeat allele. They identified 52 families based on the diagnosis of the refined phenotype of ADHD in the proband and the availability of DNA from both biological parents as well as the proband. Haplotype relative risk (HRR) analysis was performed to test a priori hypothesis and produced significant results (chi-square=4.65, P<0.035). This provides additional evidence that the DRD4 gene is associated with a refined phenotype of ADHD.
Total Sample	119 families were identified in which the proband met these criteria for a refined phenotype of ADHD. They were able to obtain blood samples, extract DNA and obtain DRD4 genotypes from 136 parents and from 105 probands. In 75 of these families, they could deduce transmission of the DRD4 alleles from 127 parents to the 75 probands. In 52 of these families, the completed information on both parents as well as the proband.
Sample Collection	ADHD probands were recruited for participation in a clinical trial being conducted at the UC Irvine Child Development Center and sponsored by ALZA Corporation or Richwood Pharmaceuticals.
Diagnosis Description	The inclusion criteria for subjects to be eligible for these clinical trials and thus to be probands in this genetic study, included a clinical diagnosis of ADHD by DSM-IV criteria confirmed by a structured interview, current treatment with typical clinical doses of methylphenidate, and absence of serious comorbid disorders. For more details, please refer to the original publication.
Technique	Blood samples were obtained when families were being seen at the UCI Child Development Center. These samples were sent to the Clarke Institute of Psychiatry, Toronto, Canada for DNA extraction. Within 3 days, genomic DNA was extracted from whole blood by salting out. The amplification of the 48-base pair repeat region of DRD4 was performed as described by Lichter et al. PCR products were separated in 3.5% agarose gels prepared with ethidium bromide and electrophoresed in 1xTBE.
Analysis Method	Genotypes were obtained from available DNA of probands and parents, and transmission of alleles from parent to proband was determined for 75 probands. In 52 of these families, genotypes were obtained on trios of the proband and both parents. The HRR test was used to calculate a within-family contingency statistic based on the alleles of the 'n' (52) trios.
Result Description	In the family-based association design, the HRR analysis of parent-to-proband allele transmission provides a test for association of an allele (7 repeat) with a disorder (ADHD), and the parental alleles are the focus of analysis. The HRR contingency statistic was significant (chi-square = 4.65, d.f.=1, P<0.035).

Other variant reported by this study (count: 1)

Genes reported by this study (count: 1)