Partial Replication of a DRD4 Association in ADHD Individuals Using a Statistically Derived Quantitative Trait for ADHD in a Family-Based Association Test

Jessica Lasky-Su, Tobias Banaschewski, Jan Buitelaar, Barbara Franke, Keeley Brookes, Edmund Sonuga-Barke, Richard Ebstein, Jacques Eisenberg, Michael Gill, Iris Manor, Ana Miranda, Fernando Mulas, Robert D. Oades, Herbert Roeyers, Aribert Rothenberger, Joseph Sergeant, Hans Christoph Steinhausen, Eric Taylor, Kaixin Zhou, Margaret ThompsonPhilip Asherson, Stephen V. Faraone

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)985-990
Number of pages6
JournalBiological Psychiatry
Volume62
Issue number9
DOIs
StatePublished - 1 Nov 2007
Externally publishedYes

Keywords

  • ADHD
  • DRD4
  • family-based association
  • hyperactive-impulsive symptoms
  • inattentive symptoms
  • PBAT

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