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Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.
Demontis, Ditte; Walters, Raymond K; Martin, Joanna; Mattheisen, Manuel; Als, Thomas D; Agerbo, Esben; Baldursson, Gísli; Belliveau, Rich; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Cerrato, Felecia; Chambert, Kimberly; Churchhouse, Claire; Dumont, Ashley; Eriksson, Nicholas; Gandal, Michael; Goldstein, Jacqueline I; Grasby, Katrina L; Grove, Jakob; Gudmundsson, Olafur O; Hansen, Christine S; Hauberg, Mads Engel; Hollegaard, Mads V; Howrigan, Daniel P; Huang, Hailiang; Maller, Julian B; Martin, Alicia R; Martin, Nicholas G; Moran, Jennifer; Pallesen, Jonatan; Palmer, Duncan S; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Poterba, Timothy; Poulsen, Jesper Buchhave; Ripke, Stephan; Robinson, Elise B; Satterstrom, F Kyle; Stefansson, Hreinn; Stevens, Christine; Turley, Patrick; Walters, G Bragi; Won, Hyejung; Wright, Margaret J; Andreassen, Ole A; Asherson, Philip; Burton, Christie L; Boomsma, Dorret I; Cormand, Bru; Dalsgaard, Søren.
Afiliação
  • Demontis D; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Walters RK; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
  • Martin J; Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
  • Mattheisen M; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Als TD; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Agerbo E; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Baldursson G; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Belliveau R; MRC Centre for Neuropsychiatric Genetics & Genomics, School of Medicine, Cardiff University, Cardiff, UK.
  • Bybjerg-Grauholm J; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Bækvad-Hansen M; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
  • Cerrato F; Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
  • Chambert K; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Churchhouse C; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
  • Dumont A; Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
  • Eriksson N; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Gandal M; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
  • Goldstein JI; Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
  • Grasby KL; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Grove J; National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
  • Gudmundsson OO; Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
  • Hansen CS; Department of Child and Adolescent Psychiatry, National University Hospital, Reykjavik, Iceland.
  • Hauberg ME; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hollegaard MV; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Howrigan DP; Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
  • Huang H; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Maller JB; Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
  • Martin AR; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Martin NG; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Moran J; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Pallesen J; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Palmer DS; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Pedersen CB; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Pedersen MG; 23andMe, Inc, Mountain View, CA, USA.
  • Poterba T; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Poulsen JB; Center for Autism Research and Treatment and Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
  • Ripke S; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Robinson EB; Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
  • Satterstrom FK; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Stefansson H; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Stevens C; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Turley P; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Walters GB; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Won H; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
  • Wright MJ; Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
  • Andreassen OA; Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
  • Asherson P; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Burton CL; Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
  • Boomsma DI; Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
  • Cormand B; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Dalsgaard S; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
Nat Genet ; 51(1): 63-75, 2019 01.
Article em En | MEDLINE | ID: mdl-30478444
ABSTRACT
Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Loci Gênicos Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Dinamarca
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Loci Gênicos Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Dinamarca