Identification of shared and differentiating genetic risk for autism spectrum disorder, attention deficit hyperactivity disorder and case subgroups

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identif...

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Detalles Bibliográficos
Autores: Mattheisen, Manuel, Grove, Jakob, Als, Thomas D., Martin, Joanna, Voloudakis, Georgios, Meier, Sandra, Demontis, Ditte, Bendl, Jaroslav, Walters, Raymond, Carrey, Caitlin E., Rosengren, Anders, Strom, Nora I., Hauberg, Mads Engel, Zeng, Biao, Hoffman, Gabriel, Bybjerg-Grauholm, J., Bækvad-Hansen, M., Agerbo, Esben, Cormand Rifà, Bru, Nordentoft, Merete, Werge, Thomas, Mors, Ole, Hougaard, David M., Buxbaum, Joseph D., Faraone, Stephen V., Franke, Barbara, Dalsgaard, Søren, Mortensen, Preben B., Robinson, Elise B., Roussos, Panos, Neale, Benjamin M., Daly, Mark J., Børglum, Anders D.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/194685
Acceso en línea:https://hdl.handle.net/2445/194685
Access Level:acceso abierto
Palabra clave:Trastorns de l'espectre autista
Trastorns per dèficit d'atenció amb hiperactivitat en els adults
Genètica humana
Autism spectrum disorders
Attention deficit disorder with hyperactivity in adults
Human genetics
Descripción
Sumario:Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.

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