Support for association between ADHD and two candidate genes: NET1 and DRD1.
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 < or = 0.009); case-control analysis revealed significant association of two DRD1 SNPs with ADHD (P < or = 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.
Bobb
Aaron J
AJ
Child Psychiatry Branch, NIMH, NIH, Bethesda, Maryland 20892-1600, USA.
Addington
Anjene M
AM
Sidransky
Ellen
E
Gornick
Michele C
MC
Lerch
Jason P
JP
Greenstein
Deanna K
DK
Clasen
Liv S
LS
Sharp
Wendy S
WS
Inoff-Germain
Gale
G
Wavrant-De Vrièze
Fabienne
F
Arcos-Burgos
Mauricio
M
Straub
Richard E
RE
Hardy
John A
JA
Castellanos
F Xavier
FX
Rapoport
Judith L
JL
D000293:Adolescent; D000294:Adolescent Behavior / Q000523:psychology; D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002652:Child Behavior / Q000523:psychology; D003071:Cognition; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D027981:Symporters / Q000235:genetics*
D050484:Norepinephrine Plasma Membrane Transport Proteins; D017447:Receptors, Dopamine D1; C493227:SLC6A2 protein, human; D027981:Symporters