Genetic Architecture of ADHD and Overlap With Other Psychiatric Disorders And Cognition-Related PhenotypesDepartment of Biomedicine/Human Genetics, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Center for Genomics and Personalized Medicine, Aarhus, Denmark; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Department of Mental Health, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
Departments of Psychiatry and of Neuroscience and Physiology, Norton College of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA.
Department of Biomedicine/Human Genetics, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Center for Genomics and Personalized Medicine, Aarhus, Denmark.
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
Departments of Cognitive Neuroscience and Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER), Instituto de Salud Carlos III, Madrid, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain; Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Catalonia, Spain.
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2023 (English)In: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 153, article id 105313Article, review/survey (Refereed) Published
Abstract [en]
Attention-deficit/hyperactivity disorder (ADHD) co-occurs with many other psychiatric disorders and traits. In this review, we summarize and interpret the existing literature on the genetic architecture of these comorbidities based on hypothesis-generating approaches. Quantitative genetic studies indicate that genetic factors play a substantial role in the observed co-occurrence of ADHD with many different disorders and traits. Molecular genetic correlations derived from genome-wide association studies and results of studies based on polygenic risk scores confirm the general pattern but provide effect estimates that are smaller than those from twin studies. The identification of the specific genetic variants and biological pathways underlying co-occurrence using genome-wide approaches is still in its infancy. The first analyses of causal inference using genetic data support causal relationships between ADHD and comorbid disorders, although bidirectional effects identified in some instances point to complex relationships. While several issues in the methodology and inferences from the results are still to be overcome, this review shows that the co-occurrence of ADHD with many psychiatric disorders and traits is genetically interpretable.
Place, publisher, year, edition, pages
Pergamon Press, 2023. Vol. 153, article id 105313
Keywords [en]
Attention-deficit/hyperactivity disorder, comorbitidy, cross-disorder genetics, genetic correlation, genome-wide association study, pleiotropy, polygenic risk score
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-107455DOI: 10.1016/j.neubiorev.2023.105313ISI: 001070941900001PubMedID: 37451654Scopus ID: 2-s2.0-85168007707OAI: oai:DiVA.org:oru-107455DiVA, id: diva2:1786580
Funder
EU, Horizon 2020, 667302 728018 2020604 101028810 848228 841899 847879 965381Novo Nordisk Foundation, NNF20OC0065561 NNF21SA0072102
Note
This research has received funding from the EU’s Horizon 2020 research and innovation program under grant agreements no. 667302 (CoCA), 728018 (Eat2beNICE) and 2020604 (TIMESPAN) and from the ECNP Network ‘ADHD across the Lifespan’ (https://www.ecnp.eu/researchinnovation/ECNP-networks/List-ECNP-Networks/). B Cormand has also been supported by the Spanish Ministerio de Ciencia, Innovaci´on y Universidades (PID2021-1277760B-I100), the Ministerio de Sanidad, Servicios Sociales e Igualdad/Plan Nacional Sobre Drogas (PNSD-2017I050), Fundaci´o La Marat´o de TV3 (202218-31), Generalitat de Catalunya/AGAUR (2021-SGR-1093), ICREA Academia 2021 and the European Union H2020 Programme (H2020/2014-2020) under grant agreements no. 841899 (GRASAD) and 101028810 (ATTENTIVE). M Ribas´es was also supported by the European Union H2020 Programme (H2020/2014–2020) under grant agreement no. 848228 (DISCOvERIE), by the Instituto de Salud Carlos III (PI20/00041, CP09/00119 and CPII15/00023), by the Pla estratègic de recerca i innovaci´o en salut (PERIS), Generalitat de Catalunya (METAL-Cat; SLT006/17/287), by the Agència de Gesti´o d’Ajuts Universitaris i de Recerca AGAUR, Generalitat de Catalunya (2017SGR1461) and by Fundaci´o La Marat´o de TV3 (202228-30, 202228-31). JA Ramos-Quiroga was also supported by the European Union H2020 Programme (H2020/2014–2020) undergrant agreement no. 848228 (DISCOvERIE). M Mitjans was supported by Horizon 2020 Marie Sklodowska-Curie Individual Fellowship from the European Commission under grant agreement no. 841899 (GRASAD), the MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU”/PRTR” (RYC2021-033573-I), Ministerio de Ciencia e Innovaci´on (PID2022-139740OA-100) and the Agència de Gesti´o d’Ajuts Universitaris i de Recerca AGAUR, Generalitat de Catalunya (2021-SGR-1093). M Soler Artigas was supported by the Instituto de Salud Carlos III (P19/01224, PI22/00464 and CP22/00128) and by the European Regional Development Fund. B Franke and A Reif were also supported by funding from the EU’s Horizon 2020 research and innovation program under grant agreement no. 847879 (PRIME). B Franke also received relevant funding from the Netherlands Organization for Scientific Research (NWO) for the GUTS project (grant 024.005.011). D Demontis is supported by the Novo Nordisk Foundation (NNF20OC0065561 and NNF21SA0072102), the Lundbeck Foundation (R344-2020-1060), the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 965381 (TIME-SPAN). AD Børglum was supported by the Lundbeck Foundation (R102-A9118, R155-2014-1724, and R248-2017-2003). Research reported in this publication was also supported by the National Institute of Mental Health of the National Institutes of Health under Award Number R01MH124851.
2023-08-092023-08-092023-10-16Bibliographically approved