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Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.
Demontis, Ditte; Walters, G Bragi; Athanasiadis, Georgios; Walters, Raymond; Therrien, Karen; Nielsen, Trine Tollerup; Farajzadeh, Leila; Voloudakis, Georgios; Bendl, Jaroslav; Zeng, Biau; Zhang, Wen; Grove, Jakob; Als, Thomas D; Duan, Jinjie; Satterstrom, F Kyle; Bybjerg-Grauholm, Jonas; Bækved-Hansen, Marie; Gudmundsson, Olafur O; Magnusson, Sigurdur H; Baldursson, Gisli; Davidsdottir, Katrin; Haraldsdottir, Gyda S; Agerbo, Esben; Hoffman, Gabriel E; Dalsgaard, Søren; Martin, Joanna; Ribasés, Marta; Boomsma, Dorret I; Soler Artigas, Maria; Roth Mota, Nina; Howrigan, Daniel; Medland, Sarah E; Zayats, Tetyana; Rajagopal, Veera M; Nordentoft, Merete; Mors, Ole; Hougaard, David M; Mortensen, Preben Bo; Daly, Mark J; Faraone, Stephen V; Stefansson, Hreinn; Roussos, Panos; Franke, Barbara; Werge, Thomas; Neale, Benjamin M; Stefansson, Kari; Børglum, Anders D.
Afiliação
  • Demontis D; Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. ditte@biomed.au.dk.
  • Walters GB; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark. ditte@biomed.au.dk.
  • Athanasiadis G; Center for Genomics and Personalized Medicine, Aarhus, Denmark. ditte@biomed.au.dk.
  • Walters R; deCODE Genetics/Amgen, Reykjavik, Iceland.
  • Therrien K; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Nielsen TT; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Farajzadeh L; Mental Health Centre Sct. Hans, Capital Region of Denmark, Institute of Biological Psychiatry, Copenhagen University Hospital, Copenhagen, Denmark.
  • Voloudakis G; Department of Evolutionary Biology, Ecology and Environmental Sciences, University of Barcelona, Barcelona, Spain.
  • Bendl J; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Zeng B; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Zhang W; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Grove J; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Als TD; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Duan J; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Satterstrom FK; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Bybjerg-Grauholm J; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Bækved-Hansen M; Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
  • Gudmundsson OO; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Magnusson SH; Center for Genomics and Personalized Medicine, Aarhus, Denmark.
  • Baldursson G; Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
  • Davidsdottir K; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Haraldsdottir GS; Center for Genomics and Personalized Medicine, Aarhus, Denmark.
  • Agerbo E; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Hoffman GE; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Dalsgaard S; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Martin J; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Ribasés M; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Boomsma DI; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Soler Artigas M; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Roth Mota N; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Howrigan D; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Medland SE; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Zayats T; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Rajagopal VM; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Nordentoft M; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Mors O; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Hougaard DM; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Mortensen PB; Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
  • Daly MJ; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Faraone SV; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
  • Stefansson H; Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
  • Roussos P; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Franke B; Center for Genomics and Personalized Medicine, Aarhus, Denmark.
  • Werge T; Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
  • Neale BM; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
  • Stefansson K; Center for Genomics and Personalized Medicine, Aarhus, Denmark.
  • Børglum AD; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nat Genet ; 55(2): 198-208, 2023 02.
Article em En | MEDLINE | ID: mdl-36702997
ABSTRACT
Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article