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Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder.
LaBianca, Sonja; Brikell, Isabell; Helenius, Dorte; Loughnan, Robert; Mefford, Joel; Palmer, Clare E; Walker, Rebecca; Gådin, Jesper R; Krebs, Morten; Appadurai, Vivek; Vaez, Morteza; Agerbo, Esben; Pedersen, Marianne Giørtz; Børglum, Anders D; Hougaard, David M; Mors, Ole; Nordentoft, Merete; Mortensen, Preben Bo; Kendler, Kenneth S; Jernigan, Terry L; Geschwind, Daniel H; Ingason, Andrés; Dahl, Andrew W; Zaitlen, Noah; Dalsgaard, Søren; Werge, Thomas M; Schork, Andrew J.
Afiliación
  • LaBianca S; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
  • Brikell I; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
  • Helenius D; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
  • Loughnan R; National Centre for Register-based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark.
  • Mefford J; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
  • Palmer CE; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
  • Walker R; Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA.
  • Gådin JR; Center for Population Neuroscience and Genetics, Laureate Institute for Brain Research, Tulsa, OK, USA.
  • Krebs M; Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Appadurai V; Center for Human Development, University of California, San Diego, La Jolla, CA, USA.
  • Vaez M; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Agerbo E; Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Pedersen MG; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
  • Børglum AD; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
  • Hougaard DM; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
  • Mors O; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
  • Nordentoft M; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
  • Mortensen PB; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
  • Kendler KS; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
  • Jernigan TL; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
  • Geschwind DH; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
  • Ingason A; National Centre for Register-based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark.
  • Dahl AW; Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
  • Zaitlen N; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
  • Dalsgaard S; National Centre for Register-based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark.
  • Werge TM; Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
  • Schork AJ; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Nat Genet ; 56(2): 234-244, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38036780
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno por Déficit de Atención con Hiperactividad / Trastorno del Espectro Autista Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno por Déficit de Atención con Hiperactividad / Trastorno del Espectro Autista Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca