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	Xu X, 201020704703
Citation	Xu X., Breen G., Chen C. K., Huang Y. S., Wu Y. Y. and Asherson P. (2010) "Association study between a polymorphism at the 3'-untranslated region of CLOCK gene and attention deficit hyperactivity disorder." Behav Brain Funct, 6: 48.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	116 probands with both parents and 64 probands with mothers only in the United Kingdom sample; 114 families with both parents, 59 families with mothers only, 39 families with fathers only in the Taiwanese sample
Predominant Ethnicity	Caucasian, Mongoloid
Population	United Kingdom, Taiwan
Gender	ninety-six percent of the sample was male subjects in the United Kingdom sample; eighty-nine percent of the sample was male in the Taiwanese sample
Age Group	Children/Adolescents : 5-15 years(mean 10.41, SD =2.34) in the United Kingdom sample; 5-15 years (mean 8.96, SD 2.60) in the Taiwanese sample

Detail Info

Summary	To investigate the association between the polymorphism (rs1801260) in ADHD, two samples of ADHD probands from the United Kingdom (n = 180) and Taiwan (n = 212) were genotyped and analysed using within family transmission disequilibrium test (TDT). Bonferroni correction procedures were used to just for multiple comparisons. They found evidence of increased transmission of the T allele of the rs1801260 polymorphism in Taiwanese samples (P-value= 0.010). There was also evidence of preferential transmission of the T allele of the rs1801260 polymorphism in combined samples from the Taiwan and United Kingdom (P-value= 0.008). This study provides evidence for the possible involvement of CLOCK in susceptibility to ADHD.
Total Sample	For the United Kingdom sample, DNA was collected from 180 DSMIV ADHD combined subtype probands, from both parents for 116 of the ADHD probands and from the mother alone for 64 of the probands; the Taiwanese sample consisted of 212 children with ADHD diagnosed between the ages of 5-15 years (mean 8.96, SD 2.60). Both parents were available for 114 families, only the mother for 59 families and only the father for 39 families.
Sample Collection	All probands were of European-Caucasian origin for the United Kingdom sample; not mentioned for the Taiwanese sample
Diagnosis Description	For the United Kingdom sample, Cases were recruited from child behaviour clinics in South-East United Kingdom and referred for assessment if they were thought by experienced clinicians to have a diagnosis of the combined subtype of ADHD under DSM-IV criteria, with no significant Axis I co-morbidity apart from oppositional defiant disorder (ODD) (5.5%) and conduct disorder (CD) (15.5%). Intelligence quotient (IQ) was assessed in the majority of the subjects using the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), but for those under 6 years, the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) was applied. For the Taiwanese sample, ADHD cases were ascertained from the Child Psychiatric Clinics in the Chang Gung Memorial Hospital in Taipei area, Taiwan. A diagnosis of ADHD was made according to DSM-IV criteria following completion of a standard maternal interview and completion of parent and teacher Conner's revised rating scales. In all 78% had the combined subtype and 22% the inattentive subtype of ADHD. With regard to co-morbidity, 4% had Tourettes syndrome and 4% oppositional defiant disorder. Autism cases were excluded from the study. No other neurological or behavioural disorders were identified.
Technique	The rs1801260 polymorphism was genotyped using the method of PCR and enzyme restriction. Genomic DNA was amplified by using the following primers: 5'- TCCAGCAGTTTCATGAGATGC-3' and 5'-GAGGTCATTTCATAGCTGAGC- 3'. The PCR products were incubated overnight at 37^oC with Bsp12861 (New United Kingdom Biolabs) and the digested PCR products were run on a 2% agarose gel containing ethidium bromide. The T allele is represented by a 221 bp fragment, and the C allele by a 125 bp and 96 bp fragments.
Analysis Method	Family genotype data were analysed using the transmission disequilibrium test (TDT) implemented in UNPHASED program (TDTPHASE). The Bonferroni correction was applied for multiple tests and P-value<0.025 was considered to show a statistically significant difference.
Result Description	TDT analysis showed that there was evidence of increased transmission of the T allele of rs1801260 SNP in the Taiwanese sample. No significant association was found between this polymorphism and ADHD in the United Kingdom sample, while combining the two datasets together the T allele of rs1801260 SNP was significantly over-transmitted to affected probands. Even after correcting P-values using the Bonferroni method for multiple tests a significant association was still found between the T allele and ADHD.

SNPs reported by this study (count: 1)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs1801260	T:C		TDT P-value=0.146, X² (1df)=2.110 for UK samples allele; TDT P-value=0.010, X² (1df)=6.701 for Taiwanese samples allele; TDT P-value=0.008, X² (1df)=7.136 for combined samples allele	increased transmission of the T allele in the Taiwanese samp...... increased transmission of the T allele in the Taiwanese samples and combined samples; no significant association in the UK sample More...	Significant

Genes reported by this study (count: 1)