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, 2005(a)15719398
Citation	Xu X., Knight J., Brookes K., Mill J., Sham P., Craig I., Taylor E. and Asherson P. (2005) "DNA pooling analysis of 21 norepinephrine transporter gene SNPs with attention deficit hyperactivity disorder: no evidence for association." Am J Med Genet B Neuropsychiatr Genet, 134B(1): 115-8.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	families with 180 probands, 334 unrelated controls
Predominant Ethnicity	Caucasian
Population	United Kingdom
Age Group	Children/Adolescents

Detail Info

Summary	This study set out to investigate whether common polymorphisms within the norepinephrine transporter gene (NET1) are associated with DSM-IV ADHD combined subtype, using a sample that has previously shown association with genes that affect the synaptic release and uptake of neurotransmitters; DAT1 and SNAP-25. They identified 21 single nucleotide polymorphisms (SNPs) from publicly available databases that had minor allele frequencies >=5% and span the NET1 genomic region, including those analyzed in previous studies of ADHD. DNA pooling was used to screen for associations using two case pools (n=180 cases) and four control pools (n=334 controls). They identified three SNPs that showed suggestive evidence for association using either case-control or within family tests of association, however, none of these were significant after adjustment for the number of markers analyzed. They conclude that none of the markers show significant evidence of association with ADHD although we cannot rule out small genetic effects.
Total Sample	DNA samples were 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. A series of 334 unrelated controls from the same ethic background were selected from an United Kingdom population sample of 8- and 9-year old twins [Trouton et al., 2002].
Sample Collection	DNA samples were 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. A series of 334 unrelated controls from the same ethic background were selected from an United Kingdom population sample of 8- and 9-year old twins [Trouton et al., 2002].
Diagnosis Description	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). Parents of referred cases 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 Conners' questionnaire [Conners, 1995].
Technique	SNP markers were screened for association using a DNA pooling approach. DNA pools were constructed by mixing equal quantities of DNA quantified to a final concentration of 5 ng/ml prior to mixing. The concentration of each DNA sample was measured using the PicoGreen dsDNA Quantitation Reagent (Cambridge Biosciences, Cambridge, United Kingdom) in a Fluorimeter (Thermo Life Sciences, Hampshire, United Kingdom).
Analysis Method	they analyzed the six SNPs identified by the chi-square comparisons by individual genotyping of DNA samples; family trio data (probands plus parents) was subsequently analyzed for the three markers using TDTPHASE; all haplotype combinations were analyzed using the-EM option of TDTPHASE
Result Description	They identified three SNPs that showed suggestive evidence for association using either case-control or within family tests of association, however, none of these were significant after adjustment for the number of markers analyzed. They conclude that none of the markers show significant evidence of association with ADHD although we cannot rule out small genetic effects.

SNPs reported by this study (count: 3)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs2242447			TDT P-value=0.07, OR=1.17	no evidence for association no evidence for association	Non-significant
rs998424			allelic X² statistic P-value=0.066, OR=1.2	no evidence for association no evidence for association	Non-significant
rs3785157			allelic X² statistic P-value=0.034, TDT P-value=0.04, OR=1.3	showed trends for association in the family sample, not sign...... showed trends for association in the family sample, not significant after adjustment for the number of markers analyzed More...	Significant

Genes reported by this study (count: 1)