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

by Hougaard, David M. , Meier, Sandra , Grove, Jakob , Als, Thomas D. , Mors, Ole , Bybjerg-Grauholm, Jonas , Bendl, Jaroslav , Voloudakis, Georgios , Franke, Barbara , Zhang, Wen , Faraone, Stephen V. , Walters, Raymond , Zeng, Biao , Demontis, Ditte , Hoffman, Gabriel , Hauberg, Mads Engel , Neale, Benjamin M. , Mattheisen, Manuel , Dalsgaard, Søren , Carey, Caitlin E. , Rosengren, Anders , Bækvad-Hansen, Marie , Roussos, Panos , Daly, Mark J. , Robinson, Elise B. , Børglum, Anders D. , Strom, Nora I. , Mortensen, Preben B. , Nordentoft, Merete , Agerbo, Esben , Buxbaum, Joseph D. , Werge, Thomas , Martin, Joanna , Cormand, Bru

in 38/39 / 38/91 / 45/43 / 631/208/1515 / 631/208/205/2138 / 692/308/2056 / Agriculture / Animal Genetics and Genomics / Attention Deficit Disorder with Hyperactivity - genetics / Attention deficit hyperactivity disorder / Autism / Autism Spectrum Disorder - genetics / Biomedical and Life Sciences / Biomedicine / Brain / Cancer Research / Chromosomes / Cognitive ability / Comorbidity / Disorders / Etiology / Gene expression / Gene Function / Genetic analysis / Genetic Predisposition to Disease / Genomes / Genomics / Human Genetics / Humans / Hyperactivity / Liability / Neurosis / Phenotype / Phenotypes / Psychopathology / Subgroups / Transcriptomes

2022

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

2022

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2022

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Journal Article

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

Hougaard, David M.,

Meier, Sandra,

Grove, Jakob,

Als, Thomas D.,

Mors, Ole,

Bybjerg-Grauholm, Jonas,

Bendl, Jaroslav,

Voloudakis, Georgios,

Franke, Barbara,

Zhang, Wen,

Faraone, Stephen V.,

Walters, Raymond,

Zeng, Biao,

Demontis, Ditte,

Hoffman, Gabriel,

Hauberg, Mads Engel,

Neale, Benjamin M.,

Mattheisen, Manuel,

Dalsgaard, Søren,

Carey, Caitlin E.,

Rosengren, Anders,

Bækvad-Hansen, Marie,

Roussos, Panos,

Daly, Mark J.,

Robinson, Elise B.,

Børglum, Anders D.,

Strom, Nora I.,

Mortensen, Preben B.,

Nordentoft, Merete,

Agerbo, Esben,

Buxbaum, Joseph D.,

Werge, Thomas,

Martin, Joanna,

Cormand, Bru

2022

Overview

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. Cross-disorder genetic association analyses identify five loci differentiating attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Individuals diagnosed with both ADHD and ASD are double-loaded with genetic risk for both disorders.

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Nature Publishing Group US,Nature Publishing Group

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38/39

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