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 -