Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.
BACKGROUND
Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals.


METHODS
Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4.


RESULTS
One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result.


CONCLUSIONS
This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.
Lasky-Su
Jessica
J
Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Banaschewski
Tobias
T
Buitelaar
Jan
J
Franke
Barbara
B
Brookes
Keeley
K
Sonuga-Barke
Edmund
E
Ebstein
Richard
R
Eisenberg
Jacques
J
Gill
Michael
M
Manor
Iris
I
Miranda
Ana
A
Mulas
Fernando
F
Oades
Robert D
RD
Roeyers
Herbert
H
Rothenberger
Aribert
A
Sergeant
Joseph
J
Steinhausen
Hans-Christoph
HC
Taylor
Eric
E
Zhou
Kaixin
K
Thompson
Margaret
M
Asherson
Philip
P
Faraone
Stephen V
SV
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D005060:Europe; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D019655:Quantitative Trait, Heritable; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012720:Severity of Illness Index
D050638:Receptors, Dopamine D4