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

A Genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts.

J. Am. Acad. Child Adolesc. Psychiatry 55, 896-905.e6 (2016)
Postprint DOI PMC
Open Access Green
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(-6) and 2.66 × 10(-6)). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. CONCLUSION: The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Adhd Symptoms ; Gwa ; Snp Heritability ; Attention Problems ; Meta-analysis; Deficit Hyperactivity Disorder; Netherlands Twin Register; Personality Consortium; Genetic Influences; Behavior Problems; Childhood; Children; Profile; Adhd; Risk
ISSN (print) / ISBN 0890-8567
e-ISSN 1527-5418
Journal Journal of the American Academy of Child and Adolescent Psychiatry
Quellenangaben Volume: 55, Issue: 10, Pages: 896-905.e6 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)