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	Qian Q, 200312627475
Citation	Qian Q., Wang Y., Zhou R., Li J., Wang B., Glatt S. and Faraone S. V. (2003) "Family-based and case-control association studies of catechol-O-methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism." Am J Med Genet B Neuropsychiatr Genet, 118B(1): 103-9.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	202 nuclear families, 340 cases, and 226 controls
Predominant Ethnicity	Mongoloid
Population	China
Gender	86.8% male
Age Group	Children/Adolescents : 6-17 years, mean age: 10.4, SD=2.6

Detail Info

Summary	TDT, HHRR, and case-control association studies were conducted within a sample of 202 nuclear ADHD families, 340 ADHD cases, and 226 controls in the Han Chinese population. Diagnoses and ADHD subtypes were ascertained according to DSM-IV criteria using USAn Clinical Diagnostic Interviewing Scales. The HHRR analysis suggested that the low enzyme-activity COMT Met allele was preferentially transmitted to ADHD boys but not girls. This association is particularly pronounced among male ADHD probands without any comorbidity, especially the ADHD-I subtype. The case-control study revealed that the Val allele was more frequent in females meeting ICD-10 or DSMIV criteria for ADHD than in female controls. Although these results suggest the COMT gene exerts some influence on the risk for ADHD in the Han Chinese population, given the potential for Type I error, these findings require replication before drawing definitive conclusions.
Total Sample	The sample consisted of 340 Chinese children between 6 and 17 years old (mean=10.4, SD=2.6), with boys accounting for 86.8% of the sample. Two hundred and two families consisted of father, mother, and affected child (trios). They also recruited a control group to allow for case-control study. The control group (n=226) was drawn from the Han population, and was comprised of healthy blood donors and individuals from our institute.
Sample Collection	ADHD cases were recruited from the child psychiatric clinics at Peking University Institute of Mental Health between September, 1999 and August, 2001.
Diagnosis Description	Consensus diagnoses were made according to USAn Clinical Diagnostic Interviewing Scales (CDIS) [Barkley, 1998], a structured interview based on the DSM-IV. To be included in the study, children had to meet three criteria: (1) meet Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, USAn Psychiatric Association, 1994) criteria for ADHD, (2) have a full scale IQ above 70 according to the Wechsler Intelligence Scale for Chinese Children, and (3) be from the Han population.
Technique	DNA was extracted from venous blood from 340 children and the biological parents of 202 children. In addition, DNA was extracted from 226 controls. DNA extraction was performed by use of the protein-depositing method. PCR amplification of the 207 base-pair (bp) fragment of COMT Val158Met was carried out on a PTC-200 thermal cycler (MJResearch, Cambridge, MA) using the following pair of primers: upstream 5'-TCG TGG ACG CCG TGA TTC AGG-3' and downstream 5'-ACA ACG GGT CAG GCA TGC A-3'.
Analysis Method	The association of COMT with ADHD was tested by two methods: (i) case-control association analysis, and (ii) family-based association analysis. In the first study, allele and genotype frequencies in different groups of subjects were compared using the Chi-Square test. For the family-based analysis, they used the transmission disequilibrium test (TDT) [Spielman et al., 1993; Ewens, 1996], and the haplotype-based haplotype relative risk (HHRR) method to avoid any potential population stratification. All statistical tests were carried out using SPSS for Windows (release 10.0). The Chi-Square test was used to assess the significance of the resulting tables.
Result Description	The HHRR analysis suggested that the low enzyme activity COMT Met allele was preferentially transmitted to ADHD boys (160 trios, x²=3.858, P=0.05, df=1) but not girls. This association is particularly pronounced among male ADHD probands without any comorbidity (50 trios, HHRR: x²=5.128, P=0.024, df=1; TDT: x²=4.558, P=0.033, df=1), especially the ADHD-I subtype (32 trios, HHRR: x²=5.792, P=0.016, df=1; TDT: x²=5.333, P=0.021, df=1). The case-control study revealed that the Val allele was more frequent in females meeting ICD-10 or DSMIV criteria for ADHD than in female controls (86 and 79.5%, respectively, x²=4.059, P=0.044, df=1). Although these results suggest the COMT gene exerts some influence on the risk for ADHD in the Han Chinese population, given the potential for Type I error, these findings require replication before drawing definitive conclusions.

SNPs reported by this study (count: 1)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs4680	Val/Met		in ADHD trios: allelic HHRR P-value=0.107, X²=2.592 for ADHD; allelic HHRR P-value=0.084, X²=2.994 for ADHDI; allelic HHRR P-value=0.44, X²=0.597 for ADHDC; allelic HHRR P-value=0.477, X²=0.505 for ADHDH; allelic TDT P-value=0.145, X²=2.124 for ADHD; allelic TDT P-value=0.118, X²=2.446 for ADHDI; allelic TDT P-value=0.55, X²=0.357 for ADHDC; allelic TDT P-value=0.727 for ADHDH; allelic chi-square P-value=0.789, X²(1df)=0.072, genotypic P-value=0.656, X²(2df)=0.842 in all cases and controls	there was no overall evidence of association between COMT Va...... there was no overall evidence of association between COMT Val158-Met and DSM-IV ADHD More...	Non-significant

Genes reported by this study (count: 1)