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

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  • dc.contributor.author Middeldorp, Christel M.
  • dc.contributor.author Vilor Tejedor, Natàlia, 1988-
  • dc.contributor.author Guxens Junyent, Mònica
  • dc.contributor.author Sunyer Deu, Jordi
  • dc.contributor.author Boomsma, Dorret I.
  • dc.date.accessioned 2019-07-04T10:32:26Z
  • dc.date.available 2019-07-04T10:32:26Z
  • dc.date.issued 2016
  • dc.description.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(-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.
  • dc.description.sponsorship This study was funded by grants from the Spanish Instituto de Salud Carlos III (CB06/02/0041, G03/176, FIS PI041436, PI081151, PI041705, PI061756, PI091958, and PS09/00432, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931 , 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, 11/02038, 13/1944, 13/2032, CP11/0178 and MS13/00054), Spanish Ministry of Science and Innovation (SAF2008-00357), European Commission (ENGAGE project and grant agreement HEALTH-F4-2007-201413, HEALTH.2010.2.4.5-1, FP7- ENV-2011 cod 282957), Fundació La Marató de TV3, Generalitat de Catalunya-CIRIT 1999SGR 00241, and Conselleria de Sanitat Generalitat Valenciana. N. Vilor-Tejedor thanks the Agència de Gestió d’Ajuts Universitaris i de Recerca - Generalitat de Catalunya for her pre-doctoral grant (2015 FI_B 00636)
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Middeldorp CM, Hammerschlag AR, Ouwens KG, Groen-Blokhuis MM, Pourcain BS, Greven CU et al. A genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts. J Am Acad Child Adolesc Psychiatry. 2016 Oct;55(10):896-905. DOI: 10.1016/j.jaac.2016.05.025
  • dc.identifier.doi http://dx.doi.org/10.1016/j.jaac.2016.05.025
  • dc.identifier.issn 0890-8567
  • dc.identifier.uri http://hdl.handle.net/10230/41940
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Journal of the American Academy of Child and Adolescent Psychiatry. 2016 Oct;55(10):896-905
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2008-00357
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282957
  • dc.rights © Elsevier http://dx.doi.org/10.1016/j.jaac.2016.05.025
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.other Trastorn per dèficit d'atenció amb hiperactivitat
  • dc.subject.other Genètica
  • dc.title A genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/acceptedVersion

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