Premium
Support for association between ADHD and two candidate genes: NET1 and DRD1
Author(s) -
Bobb Aaron J.,
Addington Anjene M.,
Sidransky Ellen,
Gornick Michele C.,
Lerch Jason P.,
Greenstein Deanna K.,
Clasen Liv S.,
Sharp Wendy S.,
InoffGermain Gale,
WavrantDe Vrièze Fabienne,
ArcosBurgos Mauricio,
Straub Richard E.,
Hardy John A.,
Castellanos F. Xavier,
Rapoport Judith L.
Publication year - 2005
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30142
Subject(s) - single nucleotide polymorphism , attention deficit hyperactivity disorder , candidate gene , atomoxetine , norepinephrine transporter , transmission disequilibrium test , snp , proband , medicine , psychology , bioinformatics , dopamine , psychiatry , genetics , gene , biology , genotype , norepinephrine , methylphenidate , mutation
Attention deficit hyperactivity disorder (ADHD) is a common, multifactorial disorder with significant genetic contribution. Multiple candidate genes have been studied in ADHD, including the norepinephrine transporter (NET1) and dopamine D1 receptor (DRD1). NET1 is implicated in ADHD because of the efficacy of atomoxetine, a selective noradrenergic reuptake inhibitor, in the treatment of ADHD. DRD1 is primarily implicated through mouse models of ADHD. DNA from 163 ADHD probands, 192 parents, and 129 healthy controls was used to investigate possible associations between ADHD and polymorphisms in 12 previously studied candidate genes ( 5‐HT1B , 5‐HT2A , 5‐HT2C , ADRA2A , CHRNA4 , COMT , DAT1 , DRD1 , DRD4 , DRD5 , NET1 , and SNAP‐25 ). Analyses included case‐control and family‐based methods, and dimensional measures of behavior, cognition, and anatomic brain magnetic resonance imaging (MRI). Of the 12 genes examined, two showed a significant association with ADHD. Transmission disequilibrium test (TDT) analysis revealed significant association of two NET1 single nucleotide polymorphisms (SNPs) with ADHD ( P ≤ 0.009); case‐control analysis revealed significant association of two DRD1 SNPs with ADHD ( P ≤ 0.008). No behavioral, cognitive, or brain MRI volume measurement significantly differed across NET1 or DRD1 genotypes at an alpha of 0.01. This study provides support for an association between ADHD and polymorphisms in both NET1 and DRD1; polymorphisms in ten other candidate genes were not associated with ADHD. Because family‐based and case‐control methods gave divergent results, both should be used in genetic studies of ADHD. © 2005 Wiley‐Liss, Inc.