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. Hottenga & 31 others J.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 journalArticle

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
LanguageEnglish
Article number10
Pages896-905
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume55
Issue number10
DOIs
StatePublished - 2016

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Middeldorp, C.M. ; Hammerschlag, A.R. ; Ouwens, K.G. ; Blokhuis, M.M. ; St. Pourcain, B. ; Greven, C.U. ; Pappa, I. ; Tiesler, C.M.T. ; 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. ; Standl, M. ; Stergiakouli, E. ; Stoltenberg, C. ; Thiering, E. ; Timpson, N.J. ; Trzaskowski, M. ; van der Most, P.J. ; Wang, C. ; Nyholt, DR ; Medland, S.E. ; Neale, B.M. ; Jacobsson, B. ; Sunyer, J. ; Hartman, C.A. ; Whitehouse, A.J.O. ; Pennell, C.E. ; Heinrich, J. ; 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. In: Journal of the American Academy of Child and Adolescent Psychiatry. 2016 ; Vol. 55, No. 10. pp. 896-905
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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",
author = "C.M. Middeldorp and A.R. Hammerschlag and K.G. Ouwens and M.M. Blokhuis and {St. Pourcain}, B. and C.U. Greven and I. Pappa and C.M.T. Tiesler and W. Ang and I.M. Nolte and N. Vilor-Tejedor and J. Bacelis and J.L. Ebejer and H. Zhao and G.E. Davies and E.A. Ehli and D.M. Evans and I.O. Fedko and M. Guxens and J.J. Hottenga and J.J. Hudziak and A. Jugessur and J.P. Kemp and E. Krapohl and N.G. Martin and M. Murcia and R. Myhre and J. Ormel and S.M. Ring and M. Standl and E. Stergiakouli and C. Stoltenberg and E. Thiering and N.J. Timpson and M. Trzaskowski and {van der Most}, P.J. and C. Wang and DR Nyholt and S.E. Medland and B.M. Neale and B. Jacobsson and J. Sunyer and C.A. Hartman and A.J.O. Whitehouse and C.E. Pennell and J. Heinrich and R. Plomin and {Davey Smith}, G. and H. Tiemeier and D. Posthuma and D.I. Boomsma",
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language = "English",
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journal = "Journal of the American Academy of Child and Adolescent Psychiatry",
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Middeldorp, CM, Hammerschlag, AR, Ouwens, KG, Blokhuis, MM, St. Pourcain, B, Greven, CU, Pappa, I, Tiesler, CMT, Ang, W, Nolte, IM, Vilor-Tejedor, N, Bacelis, J, Ebejer, JL, Zhao, H, Davies, GE, Ehli, EA, Evans, DM, Fedko, IO, Guxens, M, Hottenga, JJ, Hudziak, JJ, Jugessur, A, Kemp, JP, Krapohl, E, Martin, NG, Murcia, M, Myhre, R, Ormel, J, Ring, SM, Standl, M, Stergiakouli, E, Stoltenberg, C, Thiering, E, Timpson, NJ, Trzaskowski, M, van der Most, PJ, Wang, C, Nyholt, DR, Medland, SE, Neale, BM, Jacobsson, B, Sunyer, J, Hartman, CA, Whitehouse, AJO, Pennell, CE, Heinrich, J, Plomin, R, Davey Smith, G, Tiemeier, H, Posthuma, D & Boomsma, DI 2016, 'A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts' Journal of the American Academy of Child and Adolescent Psychiatry, vol 55, no. 10, 10, pp. 896-905. DOI: 10.1016/j.jaac.2016.05.025

A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts. / Middeldorp, C.M.; Hammerschlag, A.R.; Ouwens, K.G.; Blokhuis, M.M.; St. Pourcain, B.; Greven, C.U.; Pappa, I.; Tiesler, C.M.T.; 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.; Standl, M.; Stergiakouli, E.; Stoltenberg, C.; Thiering, E.; Timpson, N.J.; Trzaskowski, M.; van der Most, P.J.; Wang, C.; Nyholt, DR; Medland, S.E.; Neale, B.M.; Jacobsson, B.; Sunyer, J.; Hartman, C.A.; Whitehouse, A.J.O.; Pennell, C.E.; Heinrich, J.; Plomin, R.; Davey Smith, G.; Tiemeier, H.; Posthuma, D.; Boomsma, D.I.

In: Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 55, No. 10, 10, 2016, p. 896-905.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts

AU - Middeldorp,C.M.

AU - Hammerschlag,A.R.

AU - Ouwens,K.G.

AU - Blokhuis,M.M.

AU - St. Pourcain,B.

AU - Greven,C.U.

AU - Pappa,I.

AU - Tiesler,C.M.T.

AU - Ang,W.

AU - Nolte,I.M.

AU - Vilor-Tejedor,N.

AU - Bacelis,J.

AU - Ebejer,J.L.

AU - Zhao,H.

AU - Davies,G.E.

AU - Ehli,E.A.

AU - Evans,D.M.

AU - Fedko,I.O.

AU - Guxens,M.

AU - Hottenga,J.J.

AU - Hudziak,J.J.

AU - Jugessur,A.

AU - Kemp,J.P.

AU - Krapohl,E.

AU - Martin,N.G.

AU - Murcia,M.

AU - Myhre,R.

AU - Ormel,J.

AU - Ring,S.M.

AU - Standl,M.

AU - Stergiakouli,E.

AU - Stoltenberg,C.

AU - Thiering,E.

AU - Timpson,N.J.

AU - Trzaskowski,M.

AU - van der Most,P.J.

AU - Wang,C.

AU - Nyholt,DR

AU - Medland,S.E.

AU - Neale,B.M.

AU - Jacobsson,B.

AU - Sunyer,J.

AU - Hartman,C.A.

AU - Whitehouse,A.J.O.

AU - Pennell,C.E.

AU - Heinrich,J.

AU - Plomin,R.

AU - Davey Smith,G.

AU - Tiemeier,H.

AU - Posthuma,D.

AU - Boomsma,D.I.

PY - 2016

Y1 - 2016

N2 - 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

AB - 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

U2 - 10.1016/j.jaac.2016.05.025

DO - 10.1016/j.jaac.2016.05.025

M3 - Article

VL - 55

SP - 896

EP - 905

JO - Journal of the American Academy of Child and Adolescent Psychiatry

T2 - Journal of the American Academy of Child and Adolescent Psychiatry

JF - Journal of the American Academy of Child and Adolescent Psychiatry

SN - 0890-8567

IS - 10

M1 - 10

ER -