ArticleNature genetics2024
Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder.
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Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19citing papers in PubMed
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19 citing papers in PubMed, 23 citations in OpenAlex.
- Age at Diagnosis and Clinical and Genetic Profiles Among Adults With Attention-Deficit/Hyperactivity Disorder.JAMA network open · 2026Article
- Polygenic scores in psychiatric research and clinical practice.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Context-specific genetic effects inform endotypes and treatment in asthma.The Journal of allergy and clinical immunology · 2026Article
- A decade of discovery: Leveraging genomic data in the ABCD study to illuminate adolescent neurodevelopment.Developmental cognitive neuroscience · 2026Review
- Common and rare genetic variants explain distinct diagnostic variance in pediatric attention deficit hyperactivity disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Depression genetics through the lens of age at onset.Nature genetics · 2025Article
- Attention-deficit/hyperactivity disorder (ADHD) in adults: evidence base, uncertainties and controversies.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2025Article
- Fluctuating course of attention-deficit/hyperactivity disorder across development: Multifactorial influences.World journal of psychiatry · 2025Review
- Genetic risk effects on psychiatric disorders act in sets.medRxiv : the preprint server for health sciences · 2025Article
- Decomposition of phenotypic heterogeneity in autism reveals underlying genetic programs.Nature genetics · 2025Article
- Bayesian causal graphical model for joint Mendelian randomization analysis of multiple exposures and outcomes.American journal of human genetics · 2025Article
- Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research.Molecular psychiatry · 2025Review
- Factors associated with attention-deficit/hyperactivity disorder among Tunisian children.Frontiers in psychiatry · 2025Article
- Genetic liability estimated from large-scale family data improves genetic prediction, risk score profiling, and gene mapping for major depression.American journal of human genetics · 2024Article
- Connecting clinical and genetic heterogeneity in ADHD.Nature genetics · 2024Article
- Precision pharmacotherapy of atomoxetine in children with ADHD: how to ensure the right dose for the right person?Frontiers in pharmacology · 2024Review
- Factorizing polygenic epistasis improves prediction and uncovers biological pathways in complex traits.American journal of human genetics · 2023Article
- Maternal levels of acute phase proteins in early pregnancy and risk of autism spectrum disorders in offspring.Translational psychiatry · 2022Article
- Maternal Levels of Cytokines in Early Pregnancy and Risk of Autism Spectrum Disorders in Offspring.Frontiers in public health · 2022Article
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Authors and funding
27 authors at 10 institutions in 2 countries.
Sonja LaBiancaInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Isabell Brikell *The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Dorte Helenius *Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Robert Loughnan *Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA.
Joel Mefford *Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
Clare E Palmer *Center for Human Development, University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0001-8079-4071
Rebecca Walker *Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Jesper R GådinInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Morten KrebsInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.ORCID 0000-0002-4452-0732
Vivek AppaduraiInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.ORCID 0000-0002-2148-6201
Morteza VaezInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Esben AgerboThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.ORCID 0000-0002-2849-524X
Marianne Giørtz PedersenThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Anders D BørglumThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.ORCID 0000-0001-8627-7219
David M HougaardThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.ORCID 0000-0001-5928-3517
Ole MorsThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Merete NordentoftThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Preben Bo MortensenThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.ORCID 0000-0002-5230-9865
Kenneth S KendlerVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.ORCID 0000-0001-8689-6570
Terry L JerniganDepartment of Cognitive Science, University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0002-2011-9370
Daniel H GeschwindDepartment of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0003-2896-3450
Andrés IngasonInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Andrew W DahlSection of Genetic Medicine, University of Chicago, Chicago, IL, USA.ORCID 0000-0001-6520-4766
Noah ZaitlenDepartment of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
Søren DalsgaardThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.ORCID 0000-0003-4659-0969
Thomas M WergeInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark. thomas.werge@regionh.dk.ORCID 0000-0003-1829-0766
Andrew J SchorkInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark. andrew.joseph.schork@regionh.dk.ORCID 0000-0003-4164-9335
Mental Health Services · DKAarhus University · DKUniversity of California, Los Angeles · USUniversity of California San Diego · USUniversity of Copenhagen · DKAarhus University Hospital · DKStatens Serum Institut · DKTranslational Genomics Research Institute · USUniversity of Chicago · USVirginia Commonwealth University · US
Funding
Systems BiologyU19AG023122 · NIA · TRANSLATIONAL GENOMICS RESEARCH INST · PI Thomas Girke, NICHOLAS Joseph SCHORK · 2004 to 2026
$102.6MABCD-USA Consortium: Coordinating CenterU24DA041147 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SANDRA A BROWN, TERRY L. JERNIGAN · 2015 to 2026
$54.7MABCD-USA Consortium: Data Analysis, Informatics and Resource CenterU24DA041123 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANDERS M DALE · 2015 to 2026
$51.5MAdolescent Substance Use Initiation: Disentangling neurocognitive risks from consequences using longitudinal and genetically-informed methodsU01DA041120 · NIDA · UNIVERSITY OF MINNESOTA · PI Monica Luciana, Sylia Wilson · 2015 to 2026
$34.5MABCD-USA Consortium: Research ProjectU01DA041089 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Joanna Jacobus, Susan F. Tapert · 2015 to 2026
$31.7MProspective Research Studies of Maturation (PRISM)- Research ProjectU01DA041134 · NIDA · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI ERIN MCGLADE, PERRY FRANKLIN RENSHAW · 2015 to 2026
$29.2MABCD-USA CONSORTIUM: RESEARCH PROJECTU01DA041048 · NIDA · CHILDREN'S HOSPITAL OF LOS ANGELES · PI Megan Marie Herting, ELIZABETH R SOWELL · 2015 to 2026
$28.7MABCD-USA Consortium: Research ProjectU01DA041106 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mary M Heitzeg, Chandra Sekhar Sripada · 2015 to 2026
$24.9MFIU-ABCD: Pathways and Mechanisms to Addiction in the Latino Youth of South FloridaU01DA041156 · NIDA · FLORIDA INTERNATIONAL UNIVERSITY · PI Raul Gonzalez, Angela R Laird · 2015 to 2026
$22.8MABCD-USA Consortium: Research ProjectU01DA041148 · NIDA · OREGON HEALTH & SCIENCE UNIVERSITY · PI Damien A Fair, Rebekah S Huber · 2015 to 2026
$22.3MABCD-USA: NYC Research ProjectU01DA041174 · NIDA · YALE UNIVERSITY · PI Arielle Ryan Baskin-Sommers, Betty J Casey · 2015 to 2026
$19.7MAdolescent Brain Cognitive Development (ABCD) Prospective Research in Studies of Maturation (PRISM) ConsortiumU01DA041117 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI LINDA CHANG, THOMAS M ERNST · 2015 to 2026
$19.5MNHGRI NIH HHS R01 HG006399NIA NIH HHS U19 AG023122NIA NIH HHS U24 AG051129NIA NIH HHS UH2 AG064706NIA NIH HHS UH3 AG064706NIDA NIH HHS U01 DA041022NIDA NIH HHS U01 DA041028NIDA NIH HHS U01 DA041048NIDA NIH HHS U01 DA041089NIDA NIH HHS U01 DA041106NIDA NIH HHS U01 DA041117NIDA NIH HHS U01 DA041120NIDA NIH HHS U01 DA041134NIDA NIH HHS U01 DA041148NIDA NIH HHS U01 DA041156NIDA NIH HHS U01 DA041174NIDA NIH HHS U24 DA041123NIDA NIH HHS U24 DA041147NIMH NIH HHS U01 MH094432
Abstract
Attention deficit hyperactivity disorder (ADHD) is a complex disorder that manifests variability in long-term outcomes and clinical presentations. The genetic contributions to such heterogeneity are not well understood. Here we show several genetic links to clinical heterogeneity in ADHD in a case-only study of 14,084 diagnosed individuals. First, we identify one genome-wide significant locus by comparing cases with ADHD and autism spectrum disorder (ASD) to cases with ADHD but not ASD. Second, we show that cases with ASD and ADHD, substance use disorder and ADHD, or first diagnosed with ADHD in adulthood have unique polygenic score (PGS) profiles that distinguish them from complementary case subgroups and controls. Finally, a PGS for an ASD diagnosis in ADHD cases predicted cognitive performance in an independent developmental cohort. Our approach uncovered evidence of genetic heterogeneity in ADHD, helping us to understand its etiology and providing a model for studies of other disorders.
Indexed as
Attention Deficit Disorder with HyperactivityAutism Spectrum DisorderHumansMultifactorial Inheritance
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