Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
27663945
TITLE
A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts.
ABSTRACT
OBJECTIVE NlmCategory: 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 NlmCategory: METHODS
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 NlmCategory: 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 NlmCategory: CONCLUSIONS
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.
Copyright 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2016 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/12/18
revised 2016/03/25
accepted 2016/08/01
aheadofprint 2016/08/05
entrez 2016/09/25 06:00
pubmed 2016/09/25 06:00
medline 2016/09/25 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Middeldorp CM Middeldorp Christel M CM Biological Psychology, Neuroscience Campus Amsterdam, VU University Amsterdam, and GGZinGeest/VU University Medical Center, Amsterdam. Electronic address: c.m.middeldorp@vu.nl.
Hammerschlag AR Hammerschlag Anke R AR Generation R Study Group, Erasmus MC Rotterdam, the Netherlands, and Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam.
Ouwens KG Ouwens Klaasjan G KG Biological Psychology, VU University Amsterdam, and the EMGO+ Institute for Health and Care Research, VU University Medical Center.
Groen-Blokhuis MM Groen-Blokhuis Maria M MM Biological Psychology, VU University Amsterdam, and the EMGO+ Institute for Health and Care Research, VU University Medical Center.
St Pourcain B St Pourcain Beate B MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, UK, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands, and School of Experimental Psychology, University of Bristol.
Greven CU Greven Corina U CU Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Karakter, Child and Adolescent Psychiatry University Center, Radboud University Nijmegen, and MRC Social Genetic and Developmental Psychiatry Centre, King's College London.
Pappa I Pappa Irene I Generation R Study Group, and Pedagogical and Education Science, Erasmus University Rotterdam, The Netherlands.
Tiesler CM Tiesler Carla M T CM Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany and the Division of Metabolic and Nutritional Medicine, Munich, and Dr. von Hauner Children's Hospital, University of Munich Medical Center, Germany.
Ang W Ang Wei W School of Women's and Infants' Health, University of Western Australia, Perth.
Nolte IM Nolte Ilja M IM University of Groningen, University Medical Center Groningen, The Netherlands.
Vilor-Tejedor N Vilor-Tejedor Natalia N Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Universitat Pompeu Fabra (UPF), Barcelona, and CIBER Epidemiology and Public Health (CIBERESP), Madrid.
Bacelis J Bacelis Jonas J Gothenburg University, Sweden.
Ebejer JL Ebejer Jane L JL QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Zhao H Zhao Huiying H Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia.
Davies GE Davies Gareth E GE Avera Institute for Human Genetics, SD.
Ehli EA Ehli Erik A EA Avera Institute for Human Genetics, SD.
Evans DM Evans David M DM MRC IEU, School of Social and Community Medicine, and School of Social and Community Medicine, University of Bristol, and Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane.
Fedko IO Fedko Iryna O IO Biological Psychology, VU University Amsterdam.
Guxens M Guxens Mònica M CREAL, UPF, CIBERESP, and Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center-Sophia Children's Hospital, The Netherlands.
Hottenga JJ Hottenga Jouke-Jan JJ Biological Psychology, VU University, and EMGO+ Institute for Health and Care Research, VU University Medical Center.
Hudziak JJ Hudziak James J JJ Vermont Center for Children, Youth and Families and College of Medicine, University of Vermont, Burlington, and Child and Adolescent Psychiatry, Erasmus Medical Center.
Jugessur A Jugessur Astanand A Norwegian Institute of Public Health, Oslo.
Kemp JP Kemp John P JP MRC IEU, School of Social and Community Medicine, and School of Social and Community Medicine, University of Bristol, and Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane.
Krapohl E Krapohl Eva E MRC Social, Genetic and Developmental Psychiatry Centre, King's College London.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Murcia M Murcia Mario M CIBERESP, and FISABIO-Universitat Jaume I-Universitat de València Joint Research Unit of Epidemiology and Environmental Health, Valencia, Spain.
Myhre R Myhre Ronny R Norwegian Institute of Public Health, Oslo.
Ormel J Ormel Johan J Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), University Medical Center Groningen.
Ring SM Ring Susan M SM MRC IEU, School of Social and Community Medicine, and School of Social and Community Medicine, University of Bristol, and Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane.
Standl M Standl Marie M Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Stergiakouli E Stergiakouli Evie E MRC IEU.
Stoltenberg C Stoltenberg Camilla C Norwegian Institute of Public Health, Oslo.
Thiering E Thiering Elisabeth E Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany and the Division of Metabolic and Nutritional Medicine, Munich, and Dr. von Hauner Children's Hospital, University of Munich Medical Center, Germany.
Timpson NJ Timpson Nicholas J NJ MRC IEU; School of Social and Community Medicine, University of Bristol.
Trzaskowski M Trzaskowski Maciej M MRC Social, Genetic and Developmental Psychiatry Centre, King's College London.
van der Most PJ van der Most Peter J PJ University of Groningen and University Medical Center Groningen.
Wang C Wang Carol C School of Women's and Infants' Health, University of Western Australia, Perth.
EArly Genetics and Lifecourse Epidemiology (EAGLE) Consortium, Psychiatric Genomics Consortium ADHD Working Group
Nyholt DR Nyholt Dale R DR Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia.
Medland SE Medland Sarah E SE QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Neale B Neale Benjamin B Program in Medical and Population Genetics and Stanley Center for Psychiatric Genetics, Broad Institute of Massachusetts Institute of Technology, Boston, Analytic and Translation Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, and Harvard University, Cambridge, MA.
Jacobsson B Jacobsson Bo B Obstetrics and Gynecology, Gothenburg University, and the Norwegian Institute of Public Health.
Sunyer J Sunyer Jordi J CREAL, IMIM (Hospital del Mar Medical Research Institute), Barcelona, UPF, and CIBERESP.
Hartman CA Hartman Catharina A CA Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), University Medical Center Groningen.
Whitehouse AJ Whitehouse Andrew J O AJ Telethon Kids Institute, University of Western Australia, Perth.
Pennell CE Pennell Craig E CE School of Women's and Infants' Health, University of Western Australia, Perth.
Heinrich J Heinrich Joachim J Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Plomin R Plomin Robert R MRC Social, Genetic and Developmental Psychiatry Centre, King's College London.
Davey Smith G Davey Smith George G MRC IEU, and School of Social and Community Medicine.
Tiemeier H Tiemeier Henning H Epidemiology, Child and Adolescent Psychiatry, and Psychiatry, Erasmus Medical Center.
Posthuma D Posthuma Danielle D Generation R Study Group, Erasmus MC Rotterdam, the Netherlands, Child and Adolescent Psychiatry, Erasmus Medical Center, Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, and Clinical Genetics, VU University Medical Center.
Boomsma DI Boomsma Dorret I DI Biological Psychology, VU University, Neuroscience Campus Amsterdam, VU University, and EMGO+ Institute for Health and Care Research, VU University Medical Center.
INVESTIGATORS
JOURNAL
VOLUME: 55
ISSUE: 10
TITLE: Journal of the American Academy of Child and Adolescent Psychiatry
ISOABBREVIATION: J Am Acad Child Adolesc Psychiatry
YEAR: 2016
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1527-5418
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: J Am Acad Child Adolesc Psychiatry
COUNTRY: United States
ISSNLINKING: 0890-8567
NLMUNIQUEID: 8704565
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
ADHD symptoms
GWA
SNP heritability
attention problems
meta-analysis
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's