Collaborative analysis of DRD4 and DAT genotypes in population-defined ADHD subtypes.
BACKGROUND
It has been proposed that some of the variability in reporting of associations between attention deficit hyperactivity disorder (ADHD) and candidate genes may result from mixing of genetically heterogeneous forms of ADHD using DSM-IV criteria. The goal of the current study is to test whether population-based ADHD subtypes defined by latent class analysis help resolve issues of variable findings across individual gene association studies.


METHODS
Three studies which had previously reported no associations between polymorphisms of the DRD4 and DAT genes and DSM-IV defined ADHD were reanalyzed using population-based and DSM-IV defined ADHD subtypes.


RESULTS
Across studies no significant associations were found for either DRD4 or DAT polymorphisms using DSM-IV ADHD subtypes. In contrast, a significant association was found between the combined data set for the 440 base pair 3' DAT VNTR polymorphism and population-defined severe combined ADHD (OR=1.25, p=.01). A marginally significant association was also found between the 7 repeat DRD4 allele and population-defined severe combined ADHD.


CONCLUSIONS
Use of alternative population-based defined ADHD subtypes may help resolve some of the variable results presented for candidate gene association studies in ADHD.
Todd
Richard D
RD
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. toddr@psychiatry.wustl.edu
Huang
Hongyan
H
Smalley
Susan L
SL
Nelson
Stanley F
SF
Willcutt
Erik G
EG
Pennington
Bruce F
BF
Smith
Shelley D
SD
Faraone
Stephen V
SV
Neuman
Rosalind J
RJ
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D039721:Diagnostic and Statistical Manual of Mental Disorders; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D035781:Siblings; D014481:United States / Q000453:epidemiology
C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4