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. |