title: Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.
abstract: 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.
authors.affiliation: Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lasky-Su
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Jan
authors.initials: J
authors.lastname: Buitelaar
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Keeley
authors.initials: K
authors.lastname: Brookes
authors.forename: Edmund
authors.initials: E
authors.lastname: Sonuga-Barke
authors.forename: Richard
authors.initials: R
authors.lastname: Ebstein
authors.forename: Jacques
authors.initials: J
authors.lastname: Eisenberg
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Iris
authors.initials: I
authors.lastname: Manor
authors.forename: Ana
authors.initials: A
authors.lastname: Miranda
authors.forename: Fernando
authors.initials: F
authors.lastname: Mulas
authors.forename: Robert D
authors.initials: RD
authors.lastname: Oades
authors.forename: Herbert
authors.initials: H
authors.lastname: Roeyers
authors.forename: Aribert
authors.initials: A
authors.lastname: Rothenberger
authors.forename: Joseph
authors.initials: J
authors.lastname: Sergeant
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Steinhausen
authors.forename: Eric
authors.initials: E
authors.lastname: Taylor
authors.forename: Kaixin
authors.initials: K
authors.lastname: Zhou
authors.forename: Margaret
authors.initials: M
authors.lastname: Thompson
authors.forename: Philip
authors.initials: P
authors.lastname: Asherson
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
mesh_terms: 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
chemical_list: D050638:Receptors, Dopamine D4