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	Hawi Z, 2000 (b)10898900
Citation	Hawi Z., Millar N., Daly G., Fitzgerald M. and Gill M. (2000) "No association between catechol-O-methyltransferase (COMT) gene polymorphism and attention deficit hyperactivity disorder (ADHD) in an Irish sample." Am J Med Genet, 96(3): 282-4.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	94 children from 91 families
Predominant Ethnicity	Caucasian
Population	Ireland
Gender	86% males
Age Group	Children/Adolescents : aged 4-14 years

Detail Info

Summary	In this study, they hypothesised that a proportion of the genetic susceptibility to ADHD may be a consequence of dopamine depletion in the synapses due to high-level activity of the COMT gene (allele 1). Using the haplotype-based haplotype relative risk method and 94 affected children and their parents genotyped for COMT alleles, they found no significant differences in the frequency of the transmitted and nontransmitted alleles to ADHD cases from their parents. The absence of association between COMT alleles and ADHD indicated that this locus does not play a significant role or at least a role independent of other genes, in predisposing to ADHD in the Irish population.
Total Sample	Ninety-four children were assessed from 91 families. Fourteen families consisted of mother and affected child, and 80 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 occurring in approximately 90% of cases. Eighteen percent had comorbid mood disorders, 22% anxiety disorders, and 20% specific learning disabilities. Familiality was defined as the presence of one or more parents with a score on the Wender Utah Rating Scale-25 variable [Ward et al., 1993] of >36.
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 the sample and diagnosis criteria can be found in Daly et al. [1999], who used the same set of families as in the present study.
Technique	DNA was extracted from buccal cells as described in Gill et al. [1997]. Polymerase chain reaction (PCR) amplification of the region flanking the COMT 169 bp NlaIII polymorphism was achieved as described by Mynett-Johnson et al. [1998]. The PCR product was then digested using 6 units of NlaIII, as recommended by the manufacturer. Two common fragments (26 and 29 bp) and variable fragments of 114 bp (allele 1/high activity/Val 158) and 96 bp (allele 2/low activity/Met 158) are detectable. The alleles were separated on a 10% polyacrylamide gel.
Analysis Method	The haplotype-based haplotype relative risk method
Result Description	In this study, they did not observe any increase in the frequency of the high-level activity allele. Indeed, decreased transmission of the allele was observed but did not attain statistical significance at the p<0.05 level. However, result shows an almost identical number of transmitted and nontransmitted alleles in the familial and the nonfamilial cases. Furthermore, parental transmission to either males or females indicated the absence of any significant differences in the frequency of the transmitted and the nontransmitted alleles. Transmission disequilibrium test analysis has also failed to produce any evidence of association with COMT alleles. This study had a 90% power to detect an association with relative risk of 2 or more, and the study design (HHRR using trios) is not subject to the problem of ethnic stratification, which can plague case control studies.

SNPs reported by this study (count: 1)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs4680	G(Val)/A(Met)		HHRR of transmission: P-value=0.67; HHRR of familial and nonfamilial transmission: P-value=0.87 for familial, P-value=0.39 for nonfamilial; HHRR of parental transmission to male and female children: P-value=0.78 for female, P-value=0.56 for male	No association between COMT gene polymorphism and attention ...... No association between COMT gene polymorphism and attention deficit hyperactivity disorder (ADHD) in this Irish sample More...	Non-significant

Genes reported by this study (count: 1)