Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder
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 a...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/198889 |
| Acceso en línea: | https://hdl.handle.net/2445/198889 |
| Access Level: | acceso abierto |
| Palabra clave: | Trastorns per dèficit d'atenció amb hiperactivitat en els infants Trastorns per dèficit d'atenció amb hiperactivitat en els adults Genoma humà Attention deficit disorder with hyperactivity in children Attention deficit disorder with hyperactivity in adults Human genome |
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Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorderDemontis, DitteWalters, Raymond K.Martin, JoannaMattheisen, ManuelAls, Thomas D.Agerbo, EsbenBaldursson, GísliBelliveau, RichBybjerg-Grauholm, JonasBækvad-Hansen, MarieCerrato, FeliciaChambert, KimberlyChurchhouse, ClaireDumont, AshleyEriksson, NicholasGandal, MichaelGoldstein, Jacqueline I.Grasby, Katrina L.Grove, JakobGudmundsson, Olafur O.Hansen, Christine S.Hauberg, Mads EngelHollegaard, Mads V.Howrigan, Daniel P.Huang, HailiangMaller, Julian B.Martin, Alicia R.Martin, Nicholas G.Moran, JenniferPallesen, JonatanPalmer, Duncan S.Pedersen, Carsten BøckerPedersen, Marianne GiørtzPoterba, TimothyPoulsen, Jesper BuchhaveRipke, StephanRobinson, Elise B.Satterstrom, F. KyleStefansson, HreinnStevens, ChristineTurley, PatrickWalters, G. BragiWon, HyejungWright, Margaret J.ADHD Working Group of the Psychiatric Genomics Consortium (PGC)Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium23andMe Research TeamAndreassen, Ole A.Asherson, PhilipBurton, Christie L.Boomsma, Dorret I.Cormand Rifà, BruDalsgaard, SørenFranke, BarbaraGelernter, JoelGeschwind, DanielHakonarson, HakonHaavik, JanKranzler, Henry R.Kuntsi, JoannaLangley, KateLesch, Klaus-PeterMiddeldorp, ChristelReif, AndreasRhode, Luis AugustoRoussos, PanosSchachar, RussellSklar, PamelaSonuga-Barke, EdmundSullivan, Patrick F.Thapar, AnitaTung, Joyce Y.Waldman, Irwin D.Medland, Sarah E.Stefansson, KariNordentoft, MereteHougaard, David M.Werge, ThomasMors, OleMortensen, Preben BoDaly, Mark J.Faraone, Stephen V.Børglum, Anders D.Neale, Benjamin M.Trastorns per dèficit d'atenció amb hiperactivitat en els infantsTrastorns per dèficit d'atenció amb hiperactivitat en els adultsGenoma humàAttention deficit disorder with hyperactivity in childrenAttention deficit disorder with hyperactivity in adultsHuman genomeAttention 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.Nature Publishing Group2023202320192023info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion13 p.application/pdfhttps://hdl.handle.net/2445/198889Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1038/s41588-018-0269-7Nature Genetics, 2019, vol. 51, num. 1, p. 63-75https://doi.org/10.1038/s41588-018-0269-7(c) Demontis, Ditte et al., 2019info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1988892026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder |
| title |
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder |
| spellingShingle |
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder Demontis, Ditte Trastorns per dèficit d'atenció amb hiperactivitat en els infants Trastorns per dèficit d'atenció amb hiperactivitat en els adults Genoma humà Attention deficit disorder with hyperactivity in children Attention deficit disorder with hyperactivity in adults Human genome |
| title_short |
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder |
| title_full |
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder |
| title_fullStr |
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder |
| title_full_unstemmed |
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder |
| title_sort |
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder |
| dc.creator.none.fl_str_mv |
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, Felicia 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. ADHD Working Group of the Psychiatric Genomics Consortium (PGC) Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium 23andMe Research Team Andreassen, Ole A. Asherson, Philip Burton, Christie L. Boomsma, Dorret I. Cormand Rifà, Bru Dalsgaard, Søren Franke, Barbara Gelernter, Joel Geschwind, Daniel Hakonarson, Hakon Haavik, Jan Kranzler, Henry R. Kuntsi, Joanna Langley, Kate Lesch, Klaus-Peter Middeldorp, Christel Reif, Andreas Rhode, Luis Augusto Roussos, Panos Schachar, Russell Sklar, Pamela Sonuga-Barke, Edmund Sullivan, Patrick F. Thapar, Anita Tung, Joyce Y. Waldman, Irwin D. Medland, Sarah E. Stefansson, Kari Nordentoft, Merete Hougaard, David M. Werge, Thomas Mors, Ole Mortensen, Preben Bo Daly, Mark J. Faraone, Stephen V. Børglum, Anders D. Neale, Benjamin M. |
| author |
Demontis, Ditte |
| author_facet |
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, Felicia 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. ADHD Working Group of the Psychiatric Genomics Consortium (PGC) Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium 23andMe Research Team Andreassen, Ole A. Asherson, Philip Burton, Christie L. Boomsma, Dorret I. Cormand Rifà, Bru Dalsgaard, Søren Franke, Barbara Gelernter, Joel Geschwind, Daniel Hakonarson, Hakon Haavik, Jan Kranzler, Henry R. Kuntsi, Joanna Langley, Kate Lesch, Klaus-Peter Middeldorp, Christel Reif, Andreas Rhode, Luis Augusto Roussos, Panos Schachar, Russell Sklar, Pamela Sonuga-Barke, Edmund Sullivan, Patrick F. Thapar, Anita Tung, Joyce Y. Waldman, Irwin D. Medland, Sarah E. Stefansson, Kari Nordentoft, Merete Hougaard, David M. Werge, Thomas Mors, Ole Mortensen, Preben Bo Daly, Mark J. Faraone, Stephen V. Børglum, Anders D. Neale, Benjamin M. |
| author_role |
author |
| author2 |
Walters, Raymond K. Martin, Joanna Mattheisen, Manuel Als, Thomas D. Agerbo, Esben Baldursson, Gísli Belliveau, Rich Bybjerg-Grauholm, Jonas Bækvad-Hansen, Marie Cerrato, Felicia 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. ADHD Working Group of the Psychiatric Genomics Consortium (PGC) Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium 23andMe Research Team Andreassen, Ole A. Asherson, Philip Burton, Christie L. Boomsma, Dorret I. Cormand Rifà, Bru Dalsgaard, Søren Franke, Barbara Gelernter, Joel Geschwind, Daniel Hakonarson, Hakon Haavik, Jan Kranzler, Henry R. Kuntsi, Joanna Langley, Kate Lesch, Klaus-Peter Middeldorp, Christel Reif, Andreas Rhode, Luis Augusto Roussos, Panos Schachar, Russell Sklar, Pamela Sonuga-Barke, Edmund Sullivan, Patrick F. Thapar, Anita Tung, Joyce Y. Waldman, Irwin D. Medland, Sarah E. Stefansson, Kari Nordentoft, Merete Hougaard, David M. Werge, Thomas Mors, Ole Mortensen, Preben Bo Daly, Mark J. Faraone, Stephen V. Børglum, Anders D. Neale, Benjamin M. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Trastorns per dèficit d'atenció amb hiperactivitat en els infants Trastorns per dèficit d'atenció amb hiperactivitat en els adults Genoma humà Attention deficit disorder with hyperactivity in children Attention deficit disorder with hyperactivity in adults Human genome |
| topic |
Trastorns per dèficit d'atenció amb hiperactivitat en els infants Trastorns per dèficit d'atenció amb hiperactivitat en els adults Genoma humà Attention deficit disorder with hyperactivity in children Attention deficit disorder with hyperactivity in adults Human genome |
| description |
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. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2023 2023 2023 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/198889 |
| url |
https://hdl.handle.net/2445/198889 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Versió postprint del document publicat a: https://doi.org/10.1038/s41588-018-0269-7 Nature Genetics, 2019, vol. 51, num. 1, p. 63-75 https://doi.org/10.1038/s41588-018-0269-7 |
| dc.rights.none.fl_str_mv |
(c) Demontis, Ditte et al., 2019 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
(c) Demontis, Ditte et al., 2019 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
13 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Publishing Group |
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Nature Publishing Group |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Genètica, Microbiologia i Estadística) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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15.198674 |