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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	Kirley A, 200415389763
Citation	Kirley A., Lowe N., Mullins C., McCarron M., Daly G., Waldman I., Fitzgerald M., Gill M. and Hawi Z. (2004) "Phenotype studies of the DRD4 gene polymorphisms in ADHD: association with oppositional defiant disorder and positive family history." Am J Med Genet B Neuropsychiatr Genet, 131B(1): 38-42.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	178 families
Predominant Ethnicity	Caucasian
Population	Ireland
Age Group	Children/Adolescents

Detail Info

Summary	The objective of this study was to investigate association of DRD4 polymorphisms with ADHD subtypes for which there is evidence for increased heritability. The genetic variants tested were the 120 bp insertion/deletion, the -616, -521, -376, and the 48 bp DRD4 VNTR. The primary analyses were of association with oppositional defiant disorder (ODD), conduct disorder (CD), and diagnostic subtypes. Secondary analyses of clinical subtype were exploratory in nature and included analysis of association of DRD4 polymorphisms with family history of ADHD. They observed significant association between DRD4 7-repeat allele transmission and ADHD children with comorbid ODD. The DRD4 7-repeat allele was also significantly associated with family history positive ADHD. They observed no significant distortion in the transmission of any of the tested DRD4 variants with inattentive or hyperactive-impulsive subtypes or symptom dimensions.
Total Sample	One hundred and seventy eight children and their families took part in the study.
Sample Collection	178 families with clinically diagnosed ADHD children were recruited from child guidance clinics and ADHD support groups around Ireland
Diagnosis Description	To confirm DSM-IV and/or ICD-10 diagnoses of ADHD, one or both parents of each child were interviewed using the child and adolescent psychiatric assessment (CAPA) [Angold et al., 1995]. With regard to DSM-IV ADHD, 112 children (62.9%) met research criteria for ADHD combined type, 21 (11.8%) for ADHD inattentive type, and 11 (6.1%) for ADHD hyperactiveimpulsive type.
Technique	PCR amplification and genotyping methods for DRD4 markers is described in the accompanying paper by Lowe et al.
Analysis Method	Exploratory analyses were performed using a Logistic Regression based extension of the TDT (LRTDT) [Waldman et al., 1999].
Result Description	They observed significant association between DRD4 7-repeat allele transmission and ADHD children with comorbid ODD (chi(2)=6.74, df=1, P=0.01, OR=2.45) The DRD4 7-repeat allele was also significantly associated with family history positive ADHD (chi(2)=10.12, df=1, P=0.0021, OR=3.57). They observed no significant distortion in the transmission of any of the tested DRD4 variants with inattentive or hyperactive-impulsive subtypes or symptom dimensions.

Other variant reported by this study (count: 5)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DRD4 promoter duplication 120bp			allelic TDT P-value=1.0, X²=0.02 in combined subt...... allelic TDT P-value=1.0, X²=0.02 in combined subtype More...	there was no association between this variant and DSM-IV combined type ADHD	Non-significant
DRD4 promoter -376C/T			allelic TDT P-value=1.0, X²=0 in combined subtype allelic TDT P-value=1.0, X²=0 in combined subtype	there was no association between this variant and DSM-IV combined type ADHD	Non-significant
DRD4 exon3 VNTR		7R	allelic TDT P-value=0.198, X²=1.94 in all proband...... allelic TDT P-value=0.198, X²=1.94 in all probands, TDT P-value=0.098, X²=3.19 in combined subtype More...	there was no association of the DRD4 7-repeat allele in all probands and combined subtype	Non-significant
DRD4 promoter -616C/G			allelic TDT P-value=0.21, X²=1.86 in combined sub...... allelic TDT P-value=0.21, X²=1.86 in combined subtype More...	there was no association between this variant and DSM-IV combined type ADHD	Non-significant
DRD4 promoter -521C/T			allelic TDT P-value=0.33, X²=1.13 in combined sub...... allelic TDT P-value=0.33, X²=1.13 in combined subtype More...	there was no association between this variant and DSM-IV combined type ADHD	Non-significant

Genes reported by this study (count: 1)