Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
40962958
TITLE
Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes.
ABSTRACT
We performed a genome-wide association meta-analysis (GWAMA) of 290,134 attention-deficit/hyperactivity disorder (ADHD) symptom measures of 70,953 unique individuals from multiple raters, ages and instruments (ADHD ). Next, we meta-analyzed the results with a study of ADHD diagnosis (ADHD ). ADHD returned no genome-wide significant variants. We show that the combined ADHD GWAMA identified 39 independent loci, of which 17 were new. Using a recently developed gene-mapping method, Fine-mapped Locus Assessment Model of Effector genes, we identified 22 potential ADHD effector genes implicating several new biological processes and pathways. Moderate negative genetic correlations (r  < -0.40) were observed with multiple cognitive traits. In three cohorts, polygenic scores (PGSs) based on ADHD outperformed PGSs based on ADHD symptoms and diagnosis alone. Our findings support the notion that clinical ADHD is at the extreme end of a continuous liability that is indexed by ADHD symptoms. We show that including ADHD symptom counts helps to identify new genes implicated in ADHD.
© 2025. The Author(s), under exclusive licence to Springer Nature America, Inc.
DATE PUBLISHED
2025 Sep 17
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2024/03/20
accepted 2025/07/12
pubmed 2025/09/18 00:31
medline 2025/09/18 00:31
entrez 2025/09/17 23:20
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
van der Laan CM van der Laan Camiel M CM Department of Methodology and Statistics, Universiteit Utrecht, Utrecht, the Netherlands. c.m.vanderlaan@uu.nl.
Ip HF Ip Hill F HF Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Schipper M Schipper Marijn M Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Hottenga JJ Hottenga Jouke-Jan JJ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
St Pourcain B St Pourcain Beate B Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
Zayats T Zayats Tetyana T Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Pool R Pool René R Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Krapohl EML Krapohl Eva M L EML Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Brikell I Brikell Isabell I Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Soler Artigas M Soler Artigas María M Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona (UB), Barcelona, Spain.
Cabana-Domínguez J Cabana-Domínguez Judit J Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona (UB), Barcelona, Spain.
Llonga N Llonga Natalia N Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona (UB), Barcelona, Spain.
Nolte IM Nolte Ilja M IM Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Bolhuis K Bolhuis Koen K Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Palviainen T Palviainen Teemu T Institute for Molecular Medicine Finland (FIMM), HiLife, University of Helsinki, Helsinki, Finland.
Zafarmand H Zafarmand Hadi H Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Public Health Research Institute, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Gordon S Gordon Scott S QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Aliev F Aliev Fazil F Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
Burt SA Burt S Alexandra SA Department of Psychology, Michigan State University, East Lansing, MI, USA.
Wang CA Wang Carol A CA Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
Saunders G Saunders Gretchen G Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Karhunen V Karhunen Ville V Faculty of Medicine, University of Oulu, Oulu, Finland.
Adkins DE Adkins Daniel E DE Department of Psychiatry, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Border R Border Richard R Departments of Neurology and Computer Science, University of California, Los Angeles, Los Angeles, CA, USA.
Peterson RE Peterson Roseann E RE Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Prinz JA Prinz Joseph A JA Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
Thiering E Thiering Elisabeth E Ludwig-Maximilians-University of Munich, Dr. von Hauner Children's Hospital, Division of Metabolic Diseases and Nutritional Medicine, Munich, Germany.
Vilor-Tejedor N Vilor-Tejedor Natàlia N Department of Human Genetics, Radboud University Medical Center, Nijgmegen, the Netherlands.
Ahluwalia TS Ahluwalia Tarunveer S TS The Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Allegrini A Allegrini Andrea A Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Rimfeld K Rimfeld Kaili K Department of Psychology, Royal Holloway University of London, London, UK.
Chen Q Chen Qi Q Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Lu Y Lu Yi Y Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Martin J Martin Joanna J Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Bosch R Bosch Rosa R SJD MIND Schools Program, Hospital Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain.
Ramos-Quiroga JA Ramos-Quiroga Josep Antoni JA Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Neumann A Neumann Alexander A Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Ensink J Ensink Judith J Levvel, Academic Center for Child and Adolescent Psychiatry, Amsterdam, the Netherlands.
Grasby KL Grasby Katrina L KL QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Morosoli JJ Morosoli José J JJ School of Psychology, University of Queensland, Brisbane, Queensland, Australia.
Tong X Tong Xiaoran X Center for Innovation in Public Health, University of Kentucky, Lexington, KY, USA.
Marrington S Marrington Shelby S School of Public Health, The University of Queensland, Herston, Queensland, Australia.
Scott JG Scott James G JG Queensland Centre for Mental Health Research, Wacol, Queensland, Australia.
Shabalin AA Shabalin Andrey A AA Department of Psychiatry, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Corley R Corley Robin R Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Evans LM Evans Luke M LM Department of Ecology and Evolutionary Biology, University of Colorado Boulder, Boulder, CO, USA.
Sugden K Sugden Karen K Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
Alemany S Alemany Silvia S Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Sass L Sass Lærke L COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, Copenhagen, Denmark.
Vinding R Vinding Rebecca R Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Ehli EA Ehli Erik A EA Avera McKennan Hospital, Sioux Falls, SD, USA.
Hagenbeek FA Hagenbeek Fiona A FA Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
Derks EM Derks Eske M EM Translational Neurogenomics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Larsson H Larsson Henrik H School of Medical Sciences, Orebro University, Orebro, Sweden.
Snieder H Snieder Harold H Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Cecil C Cecil Charlotte C Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Whipp AM Whipp Alyce M AM Institute for Molecular Medicine Finland (FIMM), HiLife, University of Helsinki, Helsinki, Finland.
Korhonen T Korhonen Tellervo T Institute for Molecular Medicine Finland (FIMM), HiLife, University of Helsinki, Helsinki, Finland.
Vuoksimaa E Vuoksimaa Eero E Institute for Molecular Medicine Finland (FIMM), HiLife, University of Helsinki, Helsinki, Finland.
Rose RJ Rose Richard J RJ Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
Uitterlinden AG Uitterlinden André G AG Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, the Netherlands.
Haavik J Haavik Jan J K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.
Harris JR Harris Jennifer R JR Centre for Fertility and Health, The Norwegian Institute of Public Health, Oslo, Norway.
Helgeland Ø Helgeland Øyvind Ø Department of Genetics and Bioinformatics, Division of Health Data and Digitalization, The Norwegian Institute of Public Health, Bergen, Norway.
Johansson S Johansson Stefan S Department of Clinical Science, University of Bergen, Bergen, Norway.
Knudsen GPS Knudsen Gun Peggy S GPS Centre for Fertility and Health, The Norwegian Institute of Public Health, Oslo, Norway.
Njolstad PR Njolstad Pal Rasmus PR Department of Clinical Science, University of Bergen, Bergen, Norway.
Lu Q Lu Qing Q Department of Biostatistics, University of Florida, Gainesville, FL, USA.
Rodriguez A Rodriguez Alina A Department of Psychological Medicine, National University of Singapore, Singapore, Singapore.
Henders AK Henders Anjali K AK Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Mamun A Mamun Abdullah A Institute for Social Science Research, University of Queensland, Brisbane, Queensland, Australia.
Najman JM Najman Jackob M JM School of Public Health, The University of Queensland, Herston, Queensland, Australia.
Brown S Brown Sandy S Department of Psychiatry, University of California, San Diego, San Diego, CA, USA.
Hopfer C Hopfer Christian C University of Colorado School of Medicine, Aurora, CO, USA.
Krauter K Krauter Kenneth K Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.
Reynolds CA Reynolds Chandra A CA Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Smolen A Smolen Andrew A Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Stallings M Stallings Michael M Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Wadsworth S Wadsworth Sally S Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Wall TL Wall Tamara L TL Department of Psychiatry, University of California, San Diego, San Diego, CA, USA.
Eaves L Eaves Lindon L Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Silberg JL Silberg Judy L JL Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Miller A Miller Allison A Department of Pathology and Biomedical Science, and Carney Centre for Pharmacogenomics, University of Otago, Christchurch, Christchurch, New Zealand.
Havdahl A Havdahl Alexandra A Nic Waals Institute, Lovisenberg Diaconal Hospital, Oslo, Norway.
Llop S Llop Sabrina S Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Lopez-Espinosa MJ Lopez-Espinosa Maria-Jose MJ Department of Nursing, Universitat de València, Valencia, Spain.
Bønnelykke K Bønnelykke Klaus K Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Sunyer J Sunyer Jordi J CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
Arseneault L Arseneault Louise L Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Standl M Standl Marie M Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Heinrich J Heinrich Joachim J Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
Boden J Boden Joseph J Christchurch Health and Development Study, Department of Psychological Medicine, University of Otago, Christchurch, Christchurch, New Zealand.
Pearson J Pearson John J Biostatistics and Computational Biology Unit, Department of Pathology and Biomedical Science, University of Otago, Christchurch, Christchurch, New Zealand.
Horwood J Horwood John J Christchurch Health and Development Study, Department of Psychological Medicine, University of Otago, Christchurch, Christchurch, New Zealand.
Kennedy M Kennedy Martin M Department of Pathology and Biomedical Science, and Carney Centre for Pharmacogenomics, University of Otago, Christchurch, Christchurch, New Zealand.
Poulton R Poulton Richie R Dunedin Multidisciplinary Health and Development Research Unit, University of Otago, Dunedin, New Zealand.
Maes HH Maes Hermine H HH Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Hewitt J Hewitt John J Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Copeland WE Copeland William E WE Department of Psychiatry, College of Medicine, University of Vermont, Burlington, VT, USA.
Middeldorp CM Middeldorp Christel M CM Arkin Mental Health Care, Amsterdam, the Netherlands.
Williams GM Williams Gail M GM School of Public Health, The University of Queensland, Herston, Queensland, Australia.
Wray N Wray Naomi N Queensland Brain Institute, Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.
Järvelin MR Järvelin Marjo-Riitta MR Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK.
McGue M McGue Matt M Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Iacono W Iacono William W Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Caspi A Caspi Avshalom A Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Moffitt TE Moffitt Terrie E TE Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Whitehouse AJO Whitehouse Andrew J O AJO The Kids Research Institute Australia, University of Western Australia, Perth, Western Australia, Australia.
Pennell CE Pennell Craig E CE Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
Klump KL Klump Kelly L KL Department of Psychology, Michigan State University, East Lansing, MI, USA.
Jiang C Jiang Chang C Department of Biostatistics, University of Florida, Gainesville, FL, USA.
Dick DM Dick Danielle M DM College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, USA.
Reichborn-Kjennerud T Reichborn-Kjennerud Ted T Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Medland SE Medland Sarah E SE School of Psychology and Counselling, Queensland University of Technology, Brisbane, Queensland, Australia.
Vrijkotte T Vrijkotte Tanja T Department of Public and Occupational Health, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Kaprio J Kaprio Jaakko J Department of Public Health, Medical Faculty, University of Helsinki, Helsinki, Finland.
Tiemeier H Tiemeier Henning H Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Boston, MA, USA.
Davey Smith G Davey Smith George G Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Hartman CA Hartman Catharina A CA Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Oldehinkel AJ Oldehinkel Albertine J AJ Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Casas M Casas Miquel M Instituto Para el Desarrollo de Terapias Avanzadas en Neurociencias (IDETAN), Barcelona, Spain.
Ribasés M Ribasés Marta M Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona (UB), Barcelona, Spain.
Lichtenstein P Lichtenstein Paul P Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Lundström S Lundström Sebastian S Centre for Ethics, Law and Mental Health, University of Gothenburg, Gothenburg, Sweden.
Plomin R Plomin Robert R Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Bartels M Bartels Meike M Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
Nivard MG Nivard Michel G MG MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Boomsma DI Boomsma Dorret I DI Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Nature genetics
ISOABBREVIATION: Nat Genet
YEAR: 2025
MONTH: Sep
DAY: 17
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
ErratumIn Nat Genet. 2025 Sep 29. doi: 10.1038/s41588-025-02383-z. 41023451
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GENERAL NOTE
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