ADHDgene Database

Hot Results

Quick Search

Keyword:
Type:

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	Xu X, 2007(a)17328795
Citation	Xu X., Brookes K., Chen C. K., Huang Y. S., Wu Y. Y. and Asherson P. (2007) "Association study between the monoamine oxidase A gene and attention deficit hyperactivity disorder in Taiwanese samples." BMC Psychiatry, 7: 10.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	212 probands from 212 families
Predominant Ethnicity	Mongoloid
Population	Taiwan
Gender	89% males
Age Group	Children/Adolescents : aged 5-15 years

Detail Info

Summary	This study examined a 30 bp promoter variable number tandem repeat (VNTR) and a functional G/T single nucleotide polymorphism (SNP) at position 941 in exon 8 (941G/T) of MAO-A for association with ADHD in a Taiwanese sample of 212 ADHD probands. Within-family transmission disequilibrium test (TDT) was used to analyse association of MAO-A polymorphisms with ADHD in a Taiwanese population. A nominally significant association was found between the G-allele of 941G/T in MAO-A and ADHD (P-value=0.034, OR=1.57). Haplotype analysis identified increased transmission of a haplotype consisting of the 3-repeat allele of the promoter VNTR and the G-allele of the 941G/T SNP (P-value=0.045) to ADHD cases which the strong association with the G-allele drove. These findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD in the Taiwanese population. These results replicate previously published findings in a Caucasian sample.
Total Sample	The Taiwanese sample consisted of 212 children with ADHD diagnosed between the ages of 5-15 years. Both parents were available for 114 families, only the mother for 59 families and only the father for 39 families. In all 78% had the combined subtype and 22% the inattentive subtype of ADHD. With regard to comorbidity, 4% had Tourettes syndrome and 4% oppositional defiant disorder. Autism cases were excluded from the study. No other neurological or behavioural disorders were identified.
Sample Collection	ADHD cases were ascertained from Child Psychiatric Clinics in the Chang Gung Memorial Hospital in Taipei area, Taiwan.
Diagnosis Description	A diagnosis of ADHD was made according to DSM-IV criteria following completion of a standard maternal interview (kiddie-SADS, Kaufman et al.) and completion of parent and teacher Conner's revised rating scales. The subjects gave their written informed consent, and the study was approved by the Institutional Review Board, Chang Gung Memorial Hospital, Taiwan (Reference number: 94-471).
Technique	The MAO-A 30 bp-promoter VNTR was genotyped using the method described in Deckert et al.. As in previous studies the alleles of the MAO-A 30 bp VNTR were grouped into two classes (short allele: 2, 3; long allele: 3.5, 4 and 5) for the analysis based on the functional roles that the longer alleles are more active than allele 3. The 941G/T polymorphism was genotyped using Fnu4HI restriction enzyme following the protocol in Domschke et al..
Analysis Method	Family genotype data were analysed using the transmission disequilibrium test (TDT) implemented in UNPHASED. Since MAO-A is X-linked gene, genotype data from fathers was only used in the analysis of female ADHD probands. Genotype information from both parents in female probands, and from mother alone in male probands was used to analyse linkage disequilibrium (LD). An alternative haplotype analysis program, WHAP was used to test the contribution of the individual markers to the haplotype association.
Result Description	TDT analysis showed a significant increase in transmission of the G-allele of 941G/T SNP. In contrast, although the 3-repeat allele of the 30 bp VNTR was over-transmitted to affected offspring, this association was not significant in this sample. The sex specific analysis was conducted. The sex specific analysis for 941G/T SNP did not affect the association results very much (P-value=0.04 in male samples; P-value=0.56 in female samples). No significant association was found in 30 bp VNTR marker in the sex specific analysis. Moderate LD was observed between the two MAO-A markers (D'=0.62, R²=0.60). Analysis of transmission ratios for the common haplotypes of these two alleles revealed a significantly increased transmission of the 3-repeat allele of the 30 bp VNTR and the G-allele of the 941 G/T SNP to ADHD cases (3-G haplotype; P-value=0.045, OR=1.25) and decreased transmission of the common alternative 4-T haplotype (P-value=0.048). The results of WHAP analysis showed that the 30 bp VNTR could be dropped and did not make a significant contribution to the haplotype association. In contrast the 941G/T marker made a significant contribution to the haplotype association (dropping the 941G/T, P-value=0.97).

Other variant reported by this study (count: 2)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
MAOA exon8 941G/T	G/T		Single marker TDT P-value=0.034; sex specific analysis: P-va...... Single marker TDT P-value=0.034; sex specific analysis: P-value=0.04 in male, P-value=0.56 in female More...	TDT analysis showed a significant increase in transmission of the G-allele of 941G/T	Significant
MAOA promoter VNTR			Single marker TDT P-value=0.120 Single marker TDT P-value=0.120	The association was not significant	Non-significant

Genes reported by this study (count: 1)