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.
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: Benjamin M Neale; Sarah Medland; Stephan Ripke; Richard J L Anney; Philip Asherson; Jan Buitelaar; Barbara Franke; Michael Gill; Lindsey Kent; Peter Holmans; Frank Middleton; Anita Thapar; Klaus-Peter Lesch; Stephen V Faraone; Mark Daly; Thuy Trang Nguyen; Helmut Schäfer; Hans-Christoph Steinhausen; Andreas Reif; Tobias J Renner; Marcel Romanos; Jasmin Romanos; Andreas Warnke; Susanne Walitza; Christine Freitag; Jobst Meyer; Haukur Palmason; Aribert Rothenberger; Ziarih Hawi; Joseph Sergeant; Herbert Roeyers; Eric Mick; Joseph Biederman Journal: J Am Acad Child Adolesc Psychiatry Date: 2010-08-05 Impact factor: 8.829
Authors: Joseph Biederman; Carter R Petty; Kristina S Ten Haagen; Jacqueline Small; Alysa E Doyle; Thomas Spencer; Eric Mick; Michael C Monuteaux; Jordan W Smoller; Stephen V Faraone Journal: Psychiatry Res Date: 2009-11-10 Impact factor: 3.222
Authors: Ueli C Müller; Philip Asherson; Tobias Banaschewski; Jan K Buitelaar; Richard P Ebstein; Jaques Eisenberg; Michael Gill; Iris Manor; Ana Miranda; Robert D Oades; Herbert Roeyers; Aribert Rothenberger; Joseph A Sergeant; Edmund J S Sonuga-Barke; Margaret Thompson; Stephen V Faraone; Hans-Christoph Steinhausen Journal: BMC Psychiatry Date: 2011-04-07 Impact factor: 3.630
Authors: Pedro J Puentes-Rozo; Johan E Acosta-López; Martha L Cervantes-Henríquez; Martha L Martínez-Banfi; Elsy Mejia-Segura; Manuel Sánchez-Rojas; Marco E Anaya-Romero; Antonio Acosta-Hoyos; Guisselle A García-Llinás; Claudio A Mastronardi; David A Pineda; F Xavier Castellanos; Mauricio Arcos-Burgos; Jorge I Vélez Journal: Cells Date: 2019-08-16 Impact factor: 6.600
Authors: Robert D Oades; Jessica Lasky-Su; Hanna Christiansen; Stephen V Faraone; Edmund Js Sonuga-Barke; Tobias Banaschewski; Wai Chen; Richard Jl Anney; Jan K Buitelaar; Richard P Ebstein; Barbara Franke; Michael Gill; Ana Miranda; Herbert Roeyers; Aribert Rothenberger; Joseph A Sergeant; Hans-Christoph Steinhausen; Eric A Taylor; Margaret Thompson; Philip Asherson Journal: Behav Brain Funct Date: 2008-10-20 Impact factor: 3.759