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	Turic D, 2005(b)15635644
Citation	Turic D., Williams H., Langley K., Owen M., Thapar A. and O'Donovan M. C. (2005) "A family based study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD)." Am J Med Genet B Neuropsychiatr Genet, 133B(1): 64-7.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	176 parent-proband trios and 103 duos
Predominant Ethnicity	Caucasian
Population	United Kingdom
Gender	92% male and 8% female
Age Group	Children/Adolescents : 6-16 years (mean age 9.2 years, standard deviation 1.8 years)

Detail Info

Summary	The gene encoding catechol-Omethyltransferase (COMT) is an attractive candidate for ADHD susceptibility as it plays a major role in the degradation of dopamine. Moreover, a functional Val158Met polymorphism in COMT that alters the activity of the encoded protein has been strongly implicated in frontal lobe function, with the high activity Valine allele being associated with poorer performance, and ADHD is thought to involve fronto-striatal pathways. They have examined this functional variant for association with ADHD in a family based association sample comprising 279 probands and their parents. They have also examined two other markers in the COMT gene (rs737865, rs165599) which, together with the Val/Met variant, have recently been shown to be associated with altered COMT expression rather than enzyme activity. No evidence for association was observed with any single marker or haplotype in a sample of 279 affected children and their parents.
Total Sample	The sample included 176 parent-proband trios and 103 duos. ADHD probands, of whom 92% were male and 8% female, were of British Caucasian origin and aged between 6 and 16 years (mean age 9.2 years, standard deviation 1.8 years) at the time of interview.
Sample Collection	Families of children with suspected or diagnosed ADHD were recruited from District Child and Adolescent Psychiatry and Paediatric Clinics in South Wales, Bristol and the South West of United Kingdom, and Greater Manchester.
Diagnosis Description	Mothers were interviewed about their children, using the Child and Adolescent Psychiatric Assessment (CAPA) [Angold et al., 1995], a research diagnostic interview. Reports of ADHD symptoms and impairment at school were also obtained using a semi-structured teacher telephone interview (Child ADHD Teacher Telephone Interview (CHATTI) [Holmes et al., 2004]. Diagnoses were assigned according to ICD-10, DSM-IV, and DSM-III-R criteria.
Technique	DNA was obtained from venous blood or mouthwash samples using standard techniques. All three polymorphisms were genotyped by single nucleotide primer extension using a template-directed dye-terminator incorporation assay with fluorescence polarization detection [Hsu et al., 2001] based upon AcycloPrime^TM reagents (Perkin Elmer Life Science Products, Boston, MA) according to the manufacturers recommendations. Analyses were performed using a LJL Biosystems Analyst^TM platform.
Analysis Method	Genotypic data were analyzed for the complete sample using the statistical package TRANSMIT [Clayton, 1999]. However, as the use of incomplete families may lead to spurious association, they also undertook TDT analysis for complete trios only [Sham and Curtis, 1995]. Evidence for association between haplotypes constructed from the three markers and ADHD was sought using TRANSMIT.
Result Description	They have also examined two other markers in the COMT gene (rs737865, rs165599) which, together with the Val/Met variant, have recently been shown to be associated with altered COMT expression rather than enzyme activity. No evidence for association was observed with any single marker or haplotype in a sample of 279 affected children and their parents.

SNPs reported by this study (count: 3)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs4680	G(Val)/A(Met)		allelic TRANSMIT P-value (10,000 simulations)=0.88, X²=0.017	did not show preferential transmission of any allele did not show preferential transmission of any allele	Non-significant
rs165599	G/A		allelic TRANSMIT P-value (10,000 simulations)=0.71, X²=0.154	did not show preferential transmission of any allele did not show preferential transmission of any allele	Non-significant
rs737865	G/A		allelic TRANSMIT P-value (10,000 simulations)=0.52, X²=0.411	did not show preferential transmission of any allele did not show preferential transmission of any allele	Non-significant

Genes reported by this study (count: 1)