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	Langley K, 200312782968
Citation	Langley K., Payton A., Hamshere M. L., Pay H. M., Lawson D. C., Turic D., Ollier W., Worthington J., Owen M. J., O'Donovan M. C. and Thapar A. (2003) "No evidence of association of two 5HT transporter gene polymorphisms and attention deficit hyperactivity disorder." Psychiatr Genet, 13(2): 107-10.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	150 children and their parents in the family-based sample, 121 individuals in the control group
Predominant Ethnicity	Caucasian
Population	United Kingdom
Gender	52 males in the control group
Age Group	Children/Adolescents and Adults : 6-16 years for cases in the family-based sample, mean age: 44 years for controls

Detail Info

Summary	Three studies to date have found evidence (or a trend for evidence) of linkage and association between the long allele of the 44 base pair repeat insertion/deletion 5-HTT functional polymorphism (5-HTTLPR) and attention deficit hyperactivity disorder (ADHD). In an attempt to replicate these findings, they examined this polymorphism and a variable number tandem repeat in the second intron of 5-HTT for association with ADHD. One hundred and fifty children who met diagnostic criteria for ADHD and their parents (where available) were genotyped for these polymorphisms. Analysis was undertaken using the transmission disequilibrium test and haplotype analysis, as well as case-control comparisons using a control group of 121 individuals. No association between either the 5-HTTLPR or the variable number tandem repeat (VNTR) in ADHD was found. Haplotype analysis was also non-significant. Further analysis revealed no evidence of association in the subgroups of those without conduct disorder and in medication non-responders.
Total Sample	Families of children aged 6-16 years, of British Caucasian origin, with suspected ADHD were recruited from district Child and Adolescent Psychiatry Clinics (United Kingdom). One hundred and fifty children who met diagnostic criteria for ADHD and their parents (where available) were genotyped for these polymorphisms. To allow for comparison with previous work, a control group consisting of 121 British Caucasian individuals recruited from the South Wales blood transfusion service was also identified. These individuals were not screened to exclude those with psychiatric illness (52 males; mean age, 44 years; standard deviation, 11 years).
Sample Collection	Families of children aged 6-16 years, of British Caucasian origin, with suspected ADHD were recruited from district Child and Adolescent Psychiatry Clinics (United Kingdom). To allow for comparison with previous work, a control group consisting of 121 British Caucasian individuals recruited from the South Wales blood transfusion service was also identified.
Diagnosis Description	Parents were interviewed about each child using the Child and Adolescent Psychiatric Assessment (Angold et al., 1995), a semi-structured, interviewer-based diagnostic interview. The presence of ADHD symptoms in more than one setting was confirmed using a semi-structured teacher telephone interview that has been shown to have good test-re-test reliability and validity. Diagnoses were assigned according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R/DSM-IV and ICD-10 criteria.
Technique	DNA was extracted from blood samples and mouth swabs, and genotyping was undertaken using standard laboratory protocols previously described in Payton et al. (2001). Genotyping of the 5-HT transporter 44 base pair insertion/deletion transcription initiation site (Lesch et al., 1996) and the 17 base pair repeat intron 2 (Ogilvie et al., 1996) was undertaken successfully for 150 affected individuals.
Analysis Method	Analysis of preferential transmission for the two polymorphisms was performed using the Extended TDT (ETDT) (Sham and Curtis, 1995) and TRANSMIT (Clayton, 1999) statistical packages. Haplotype analysis was performed using TRANSMIT and HAPMAX (Krawczak et al., 1988). To allow for comparison with previous work, they also conducted case-control analysis using an inhouse statistical package (JWOOLF) to assess odds ratios.
Result Description	No association between either the 5-HTTLPR or the variable number tandem repeat (VNTR) in ADHD was found (extended transmission disequilibrium test; P=0.37 and P=0.62, respectively). Haplotype analysis was also non-significant. Further analysis revealed no evidence of association in the subgroups of those without conduct disorder and in medication non-responders.

Other variant reported by this study (count: 2)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
5HTTLPR	short/long		allelic ETDT P-value=0.37, X²=0.82 in the total s...... allelic ETDT P-value=0.37, X²=0.82 in the total sample; allelic ETDT P-value=0.82, X²=0.049, OR=1.04 in the case-control analysis More...	there was no evidence of preferential transmission of the long allele in the total sample and case-control differences were also not significant	Non-significant
SLC6A4 intron2 VNTR			ETDT P-value=0.619, X²=0.248 for allele 10, ETDT ...... ETDT P-value=0.619, X²=0.248 for allele 10, ETDT P-value=0.763, X²=0.091 for allele 12, TRANSMIT P-value=0.516 in the total sample; allelic P-value=0.14, X²=2.14, OR=0.992 in the case-control analysis More...	no significant preferential transmission was found in the total sample, and no significant differences were found when clumped alleles 9 and 10 for the case-control analysis	Non-significant

Genes reported by this study (count: 1)