Study Report
Basic Info
Reference |
Xu X, 201020704703
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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.
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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
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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
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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 37oC 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 |
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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...
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Significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
CLOCK |
T allele of rs1801260 was significantly over-transmitted in ......
T allele of rs1801260 was significantly over-transmitted in the Taiwanese samples and combined samples even after Bonferroni correction, possible involvement of CLOCK in susceptibility to ADHD
More...
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Significant
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