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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	Manor I, 200011121197
Citation	Manor I., Kotler M., Sever Y., Eisenberg J., Cohen H., Ebstein R. P. and Tyano S. (2000) "Failure to replicate an association between the catechol-O-methyltransferase polymorphism and attention deficit hyperactivity disorder in a second, independently recruited Israeli cohort." Am J Med Genet, 96(6): 858-60.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	70 nuclear families
Predominant Ethnicity	Jews
Population	Israel
Age Group	Children/Adolescents : mean age 10 years (SD=0.94)

Detail Info

Summary	They previously reported an association in 48 ADHD triads (both parents and proband) between the catechol-O-methyl-transferase (COMT) polymorphism (especially the high enzyme activity val allele) and the Diagnostic and Statistical Manual. In the current report, they attempted to replicate this finding in an independently recruited group of 70 nuclear families using the haplotype relative risk design. In the current investigation, no evidence for association of the COMT polymorphism and ADHD (or any of the DSM IV subtypes) was observed in either the current cohort or the expanded cohort of 118 Israeli triads.
Total Sample	An independently recruited group of 70 nuclear families was used in this study. The percentage of probands with ADHD combined was 81% and inattentive 19%.
Sample Collection	ADHD subjects and their families were recruited consecutively (~85% of the parents agreed to participate) for participation in this study from the ADHD unit in the Children and Adolescents Division of Geha Mental Health Center that primarily serves the central part of Israel (greater municipal Tel-Aviv area). Triad families included all diagnosed ADHD children who had two biological parents, and included both Ash-kenazi and non-Ashkenazi Jews. The Ethics Committee of the Israeli Health Ministry approved this study, and written informed consent was obtained from participating subjects.
Diagnosis Description	ADHD diagnosis followed DSM IV guidelines that recognizes three types of ADHD: ADHD, predominantly inattentive (type I), ADHD, predominantly hyperactive impulse (type II), and ADHD, combined type (III). The informants were the parents, the teacher, and the proband. An experienced psychiatrist using an interview based on DSM-IV criteria for ADHD and conduct disorder interviewed the parents and the proband. When available, teachers were also informants and along with parents were interviewed using two instruments: the abbreviated Conners Rating Scales and the Child Behavior Check List . A positive diagnosis was made only if there was a reasonable consensus between the parent and teacher regarding the Conners questionnaire. Probands were also administered the Test of Variables of Attention (TOVA). The continuous performance test was not used diagnostically. Cases were excluded with a primary diagnosis of pervasive developmental disorder; physically handicapped; psychosis; mental retardation; epilepsy; hyperthyroidism; evidence or history of child abuse; and adoption. Children with an IQ less than 80 determined by the Wechsler Intelligence Scale for Children (WICS) were excluded.
Technique	Characterization of the COMT polymorphism was carried out as previously described [Eisenberg et al., 1999].
Analysis Method	The robust family-based haplotype relative risk (HRR) design was used to test association between ADHD and the COMT polymorphism All statistical tests were carried out using SPSS for Windows.
Result Description	No association was observed between ADHD and the COMT polymorphism in a new group of 70 ADHD triads when either allele or genotype frequency was examined. Nor was any association observed in the subgroup of DSM IV combined ADHD subtype (excluding inattention) probands or in a subgroup of triads where the proband showed a positive T.O.V.A. response to Ritalin. Finally no association is observed in the expanded group of 118 triads either in the entire cohort or in the subgroup of DSM IV combined type.

SNPs reported by this study (count: 1)

Genes reported by this study (count: 1)