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	Hawi Z, 2000 (a)10898897
Citation	Hawi Z., McCarron M., Kirley A., Daly G., Fitzgerald M. and Gill M. (2000) "No association of the dopamine DRD4 receptor (DRD4) gene polymorphism with attention deficit hyperactivity disorder (ADHD) in the Irish population." Am J Med Genet, 96(3): 268-72.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	97 children from 99 families
Predominant Ethnicity	Caucasian
Population	Ireland
Gender	85% males
Age Group	Children/Adolescents : aged 4-14 years

Detail Info

Summary	In this study they investigated 78 ADHD parent proband trios and 21 parent proband pairs for the transmission of the DRD4 alleles in HHRR and case control design. They found no significant differences in the frequency of the DRD4 alleles transmitted or not transmitted to ADHD cases from their parents nor when comparing case allele frequencies to ethnically matched controls. Therefore, it is unlikely that the DRD4 7-repeat allele is associated with ADHD in the Irish population.
Total Sample	Ninety-seven children were assessed from 99 families. Twenty-one families consisted of mother and affected child, and 78 families consisted of mother, father, and affected child (trios). Approximately 80% of the children in this study with ADHD also met diagnostic criteria for other disorders, with oppositional defiant disorder and conduct disorder representing 90% of comorbidity. Eighteen percent had comorbid mood disorders, 22% had anxiety disorders, and 20% had specific learning disabilities.
Sample Collection	ADHD cases were recruited from child psychiatric clinics and schools in West County Dublin and from the Hyperactive and Attention Deficit Children's Support Group of Ireland. The families were ethnically Irish with the exception of two families (in one the father was Arabian, and in the other the father was Croatian).
Diagnosis Description	Details of diagnosis and clinical criteria can be found in Daly et al. [1999]. Briefly, consensus diagnoses were made according to DSM-IV ADHD or UADD either with or without comorbidity. These diagnoses were based on all available clinical information and the rating scales described below. The rating scales used were (1) the Child Behavioral Checklist (CBCL), a widely based behavioral symptom measure and the records of child behavior problems and social competencies as reported by parents; (2) the Connors Parents and Teachers Rating Scales, which are 48-item parent and 39-item teacher rating scales; (3) the Comprehensive Teachers Rating Scale (ACTeRS), which include 24 items relevant to classroom behavior. The 25-item Wender-Utah Rating Scale (WURS) [Ward et al., 1993] was applied to all parents. This rating scale seeks to retrospectively make a diagnosis of ADHD during childhood. A cutoff score of 36 or higher is 96% sensitive and 96% specific for adults with ADHD as children [Ward et al., 1993]. Familiality, for the purposes of the present study, was defined as the presence of one or more parents with a score on the Wender of >36.
Technique	PCR amplification of the highly GC rich polymorphic 48-bp repeat region of the DRD4 gene was achieved as described by Adamson et al. [1995]. Depending on the quality of the amplification, approximately 10 ul PCR product was loaded on a 6% nondenaturing polyacrylamide gel. For details about silver staining, please refer to the original publication.
Analysis Method	In this study, the haplotype-based haplotype relative risk (HHRR) design was used to avoid any potential population stratification. In this method, the non-transmitted parental alleles are used as controls for evaluating allele transmission. Alleles are identified as transmitted or not transmitted and tabulated. The X² test was used to assess the significance of the resulting tables. Allele frequencies in the ADHD children were additionally compared with frequencies from a control sample drawn from blood donors and compared using a X² test.
Result Description	Seven different repeat alleles were detected in both the proband and parental sample. The distribution of allele frequencies are consistent with those reported for mixed Caucasian and North USAn populations [Chang et al., 1996] and were no different from an Irish control sample. For the 7-repeat alleles where transmission from parents could be identified, the allele was transmitted 37 times and was not transmitted 33 times (P=0.95). Similarly, almost equal frequencies were observed for all other DRD4 allele transmitted or not transmitted. In addition, almost identical frequencies were observed when alleles were divided into short (2-4) repeats or long (5-8) repeats (P=0.95). When cases were divided by sex, a nonsignificant excess of transmission of the 7-repeat allele (10 transmissions vs. 6 nontransmissions) was observed for female cases. Analyzing family history-positive families (those where at least one parent scored >=36 on the Wender scale) also showed no significant differences in the frequency of DRD4 alleles.

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DRD4 exon3 VNTR	2-8 repeat; short(2-4)/long(5-8)		HHRR P-value=0.95 for allele 7-repeat; P-value=0.95 when com...... HHRR P-value=0.95 for allele 7-repeat; P-value=0.95 when comparing short repeats and long repeats More...	no significant evidence for biased transmission	Non-significant

Genes reported by this study (count: 1)