Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
DNA pooling analysis of 21 norepinephrine transporter gene SNPs with attention deficit hyperactivity disorder : no evidence for association. / Xu, Xiaohui; Knight, Jo; Brookes, Keeley et al.
In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics , Vol. 134B, No. 1, 05.04.2005, p. 115-118.Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - DNA pooling analysis of 21 norepinephrine transporter gene SNPs with attention deficit hyperactivity disorder
T2 - no evidence for association
AU - Xu, Xiaohui
AU - Knight, Jo
AU - Brookes, Keeley
AU - Mill, Jonathan
AU - Sham, Pak
AU - Craig, Ian
AU - Taylor, Eric
AU - Asherson, Philip
N1 - Copyright 2005 Wiley-Liss, Inc.
PY - 2005/4/5
Y1 - 2005/4/5
N2 - The norepinephrine system is known to play a role in attentional and cognitive-energetic mechanisms and is thought to be important in attention deficit hyperactivity disorder (ADHD). Stimulant medications are known to alter the activity of norepinephrine as well as dopamine in the synapse and the highly selective norepinephrine reuptake inhibitor, atomoxetine, is an effective treatment for ADHD symptoms. 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. We identified 21 single nucleotide polymorphisms (SNPs) from publicly available databases that had minor allele frequencies > or =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). We 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. We conclude that none of the markers show significant evidence of association with ADHD although we cannot rule out small genetic effects.
AB - The norepinephrine system is known to play a role in attentional and cognitive-energetic mechanisms and is thought to be important in attention deficit hyperactivity disorder (ADHD). Stimulant medications are known to alter the activity of norepinephrine as well as dopamine in the synapse and the highly selective norepinephrine reuptake inhibitor, atomoxetine, is an effective treatment for ADHD symptoms. 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. We identified 21 single nucleotide polymorphisms (SNPs) from publicly available databases that had minor allele frequencies > or =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). We 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. We conclude that none of the markers show significant evidence of association with ADHD although we cannot rule out small genetic effects.
KW - Algorithms
KW - Alleles
KW - Attention Deficit Disorder with Hyperactivity
KW - DNA
KW - Databases, Nucleic Acid
KW - Gene Frequency
KW - Heterozygote
KW - Humans
KW - Norepinephrine Plasma Membrane Transport Proteins
KW - Odds Ratio
KW - Polymorphism, Single Nucleotide
KW - Symporters
U2 - 10.1002/ajmg.b.30160
DO - 10.1002/ajmg.b.30160
M3 - Journal article
C2 - 15719398
VL - 134B
SP - 115
EP - 118
JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
SN - 1552-4841
IS - 1
ER -