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	Eisenberg J, 199910490706
Citation	Eisenberg J., Mei-Tal G., Steinberg A., Tartakovsky E., Zohar A., Gritsenko I., Nemanov L. and Ebstein R. P. (1999) "Haplotype relative risk study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD): association of the high-enzyme activity Val allele with ADHD impulsive-hyperactive phenotype." Am J Med Genet, 88(5): 497-502.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	48 ADHD probands and their parents
Predominant Ethnicity	Ashkenazi Jews, non-Ashkenazi Jews
Population	Israel
Gender	40 males and eight females
Age Group	Children/Adolescents : 5-17 years (average age=9.4, SD=2.5)

Detail Info

Summary	In the current investigation, a catechol-O-methyltransferase (COMT) polymorphism that codes for a high versus low enzyme COMT activity was examined using family-based methods for a role in ADHD. Using a haplotype relative risk design and a parent-to-proband allele transmission test with 48 ADHD triads, they found an association between COMT and illness. In particular, the impulsive-hyperactive type of ADHD (excluding inattention) ascertained by Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria, by the Conners Teaching Rating Hyperactivity scale as well as by the Continuous Performance Test False Alarm scale were associated with the high enzyme activity COMT val allele. Similar results were obtained if genotype frequencies were compared. It should be noted that the association between the high-enzyme activity COMT val allele that increases CNS dopamine (and norepinephrine) clearance is consistent with the use of methylphenidate, an agent that increases dopamine (and norepinephrine) turnover, in the treatment of this disorder. These provisional findings suggest that newly developed COMT inhibitors such as tolcapone, applied in Parkinson's disease, might in due time be considered in the treatment of ADHD.
Total Sample	The probands consisted of 40 males and eight females from 46 families. The average age was 9.4 years, SD 2.5 (range 5-17 years). The percentage of probands with ADHD combined type was 57%, inattentive 33%, impulsive 10%. Among probands participating in the study 39% met criteria for comorbid oppositional defiance disorder or conduct disorder. Transient tics were displayed in 18% of the probands.
Sample Collection	ADHD subjects and their families were recruited for participation in this study from a child psychiatry unit in a community mental health center and from several child neurology clinics in the Jerusalem municipal area.
Diagnosis Description	The criteria for eligibility included Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria according to the K-SAD-PL (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version) [Shanee, 1966].
Technique	DNA was extracted from frozen blood using a Qiamp kit (Qiagen, Germany). Each individual was typed for high and low COMT activity (val/met polymorphism) by amplification of a 169 base pair fragment by using PCR.
Analysis Method	family-based HRR design by using SPSS for Windows
Result Description	They found an association between COMT and illness (X² = 4.72, p = 0.03, df = 1). In particular, the impulsive-hyperactive type of ADHD (excluding inattention) ascertained by Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria (X² = 8.34, p = 0.004, df = 1), by the Conners Teaching Rating Hyperactivity scale (Pearson X² = 5.32, p = 0.02, df = 1) as well as by the Continuous Performance Test False Alarm scale (X² = 2.78, p = 0.096, df = 1) were associated with the high enzyme activity COMT val allele. Similar results were obtained if genotype frequencies were compared.

SNPs reported by this study (count: 1)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs4680	Val/Met		HRR P-value=0.03, X²=4.72, df=1 for the transmission of high enzyme activity COMT val allele to ADHD probands; HRR P-value=0.004, X²=8.34, df=1 for the transmission of high enzyme activity COMT val allele to impulsive or combined-type probands; HRR P-value=1.0, X²=0.000, df=1 between COMT allele frequency and inattentive type probands	The results of HRR analysis showed significant association b...... The results of HRR analysis showed significant association between COMT val allele and ADHD and impulsive or combined-type ADHD. More...	Significant

Genes reported by this study (count: 1)