A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts

C.M. Middeldorp, A.R. Hammerschlag, K.G. Ouwens, M.M. Blokhuis, B. St. Pourcain, C.U. Greven, I. Pappa, C.M.T. Tiesler, W. Ang, I.M. Nolte, N. Vilor-Tejedor, J. Bacelis, J.L. Ebejer, H. Zhao, G.E. Davies, E.A. Ehli, D.M. Evans, I.O. Fedko, M. Guxens, J.J. HottengaJ.J. Hudziak, A. Jugessur, J.P. Kemp, E. Krapohl, N.G. Martin, M. Murcia, R. Myhre, J. Ormel, S.M. Ring, M. Standl, E. Stergiakouli, C. Stoltenberg, E. Thiering, N.J. Timpson, M. Trzaskowski, P.J. van der Most, C. Wang, DR Nyholt, S.E. Medland, B.M. Neale, B. Jacobsson, J. Sunyer, C.A. Hartman, A.J.O. Whitehouse, C.E. Pennell, J. Heinrich, R. Plomin, G. Davey Smith, H. Tiemeier, D. Posthuma, D.I. Boomsma

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Objective The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46 × 10
Original languageEnglish
Article number10
Pages (from-to)896-905
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume55
Issue number10
DOIs
Publication statusPublished - 2016

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