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, 2007(b)17044097
Citation	Xu X., Mill J., Zhou K., Brookes K., Chen C. K. and Asherson P. (2007) "Family-based association study between brain-derived neurotrophic factor gene polymorphisms and attention deficit hyperactivity disorder in UK and Taiwanese samples." Am J Med Genet B Neuropsychiatr Genet, 144B(1): 83-6.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	180 ADHD probands for United Kingdom sample, 212 ADHD probands for Taiwanese sample
Predominant Ethnicity	Caucasian, Mongoloid
Population	United Kingdom, Taiwan
Gender	96% males for United Kingdom, 89% males for Taiwanese
Age Group	Children/Adolescents : aged 5-15 years, mean age 10.41 years (SD=2.34) for United Kingdom; aged 5-15 years, mean age 8.96 years (SD=2.60) for Taiwanese

Detail Info

Summary	This study investigated the role of two common BDNF variants (Val66Met, C270T) in two samples of ADHD probands from the United Kingdom (n=180) and Taiwan (n=212). They found evidence of increased transmission of the C allele of the C270T in Taiwanese samples (P-value=0.009) and the two samples pooled together (P-value=0.007). No association was found between the Val66Met polymorphism and ADHD in either of the two populations. Analysis of haplotypes demonstrated a significant decreased transmission of haplotypes containing the Val66 allele and the C270T allele in the Taiwanese samples (P-value=0.032) and the pooled sample set (P-value=0.016). This study provides evidence for the possible involvement of BDNF in susceptibility to ADHD.
Total Sample	For the United Kingdom sample, DNA was collected from 180 DSM-IV ADHD combined subtype probands, from both parents for 116 of the ADHD probands and from the mother alone for 64 of the probands. For the Taiwanese sample, DNA sample was collected from 212 DSM-IV ADHD probands, from both parents for 135 of the ADHD probands and from the mother alone for 35 of the probands. For the Taiwanese sample, 78% had the combined type and 22% the inattentive subtype of ADHD with no co-morbid disorders apart from oppositional defiant disorder; conduct disorder, and possible Tourettes syndrome in four cases. 13% had IQ between 50 and 69 (87%>69).
Sample Collection	For the United Kingdom sample, cases were recruited from child behavior clinics in South-East United Kingdom. All probands were of European-Caucasian origin. For the Taiwanese sample, cases were ascertained from child psychiatric clinics in the Chang Gung Memorial Hospital in Taipei area, Taiwan.
Diagnosis Description	For the United Kingdom sample, cases were 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) and conduct disorder (CD) and IQ greater than 70. Only those individuals fulfilling the recruitment criteria after completion of research assessments were included in the study. Parents were interviewed with a modified version of the Child and Adolescent Psychiatric Assessment (CAPA) [Angold et al., 1995]. Information on ADHD symptoms at school was obtained using the long form of the Conner's questionnaire [Conners, 1995]. HYPESCHEME data sheets were completed using these data plus review of case notes. HYPESCHEME diagnoses were checked against researcher applied DSM-IV criteria and discrepancies reviewed by two researchers. Where consensus could not be reached, cases were brought to case conference and final consensus agreement made with a senior clinical researcher. For the Taiwanese sample, following completion of a standard maternal interview, the Kiddie-SADS [Kaufman et al., 1997] and completion of parent and teacher Conner's revised rating scales [Conners, 1995] diagnosis was applied according to DSM-IV criteria.
Technique	Two SNPs in the BDNF gene were genotyped using enzyme restriction as previously described. The Val66Met SNP changes a PmlI restriction site [Matsushita et al., 2005] and the C270T SNP changes a HinfI restriction site [Kunugi et al., 2001].
Analysis Method	Genotype data were analyzed using the transmission disequilibrium test (TDT) [Spielman et al., 1993], the haplotype-based haplotype relative risk test (HHRR) [Terwilliger and Ott, 1992], and TRANSMIT for the analysis of haplotypes [Clayton, 1999].
Result Description	Significant LD was found between the two markers in both United Kingdom and Taiwanese samples. For SNP Val66Met, no significant preferential transmission of any allele was found in either United Kingdom samples or Taiwanese samples. Furthermore, there was no evidence of preferential parental transmission in the two populations. For SNP C270T, there was evidence of increased transmission of the C allele in the Taiwanese sample. There was also a weak non-significant trend for association of the same allele in the United Kingdom sample, while combining the two datasets together also gave significant evidence for association.

SNPs reported by this study (count: 1)

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
BDNF C270T	C/T		UK sample: TDT P-value=0.176, HHRR P-value=0.180, TRANSMIT P...... UK sample: TDT P-value=0.176, HHRR P-value=0.180, TRANSMIT P-value=0.686; Taiwanese sample: TDT P-value=0.009, HHRR P-value=0.008, TRANSMIT P-value=0.008; Combined sample: TDT P-value=0.007, HHRR P-value=0.007, TRANSMIT P-value=0.037 More...	there was evidence of increased transmission of the C allele in the Taiwanese sample and combined sample.	Significant

Genes reported by this study (count: 1)