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Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups
Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
DOI
- https://doi.org/10.1038/s41588-022-01171-3
Final published version
- Manuel Mattheisen, Dalhousie University, Ludwig Maximilian University of Munich, iSEQ - Centre for Integrative Sequencing ,
- Jakob Grove
- Thomas D Als
- Joanna Martin, Cardiff Metropolitan University ,
- Georgios Voloudakis, Icahn School of Medicine at Mount Sinai ,
- Sandra Meier
- Ditte Demontis
- Jaroslav Bendl, Icahn School of Medicine at Mount Sinai ,
- Raymond Walters, Harvard University, Broad Institute ,
- Caitlin E Carey, Broad Institute, Harvard University ,
- Anders Rosengren, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, University of Copenhagen ,
- Nora I Strom, Ludwig Maximilian University of Munich, Karolinska Institutet, iSEQ - Centre for Integrative Sequencing ,
- Mads Engel Hauberg, Icahn School of Medicine at Mount Sinai ,
- Biao Zeng, Icahn School of Medicine at Mount Sinai ,
- Gabriel Hoffman, Icahn School of Medicine at Mount Sinai ,
- Wen Zhang, Icahn School of Medicine at Mount Sinai ,
- Jonas Bybjerg-Grauholm, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Statens Serum Institut ,
- Marie Bækvad-Hansen, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Statens Serum Institut ,
- Esben Agerbo
- Bru Cormand, University of Barcelona ,
- Merete Nordentoft, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, University of Copenhagen, Capitol Region of Denmark ,
- Thomas Werge, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, University of Copenhagen ,
- Ole Mors
- David M Hougaard, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Statens Serum Institut ,
- Joseph D Buxbaum, Icahn School of Medicine at Mount Sinai ,
- Stephen V Faraone, SUNY Upstate Medical University ,
- Barbara Franke, Radboud University Nijmegen ,
- Søren Dalsgaard
- Preben B Mortensen
- Elise B Robinson, Harvard University, Broad Institute ,
- Panos Roussos, Icahn School of Medicine at Mount Sinai ,
- Benjamin M Neale, Harvard University, Broad Institute ,
- Mark J Daly, Broad Institute, University of Helsinki, Harvard University ,
- Anders D Børglum
- Department of Biomedicine - Department of Human Genetics
- Department of Molecular Biology and Genetics - Bioinformatics Research Centre (BiRC)
- National Centre for Register-based Research
- National Centre for Register-based Research - CIRRAU - Centre for Integrated Register-based Research
- Department of Political Science - Platform for Inequality Research at Aarhus University (PIREAU)
- Department of Clinical Medicine - Psychosis Research Unit
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.
| Original language | English |
|---|---|
| Journal | Nature Genetics |
| Volume | 54 |
| Issue | 10 |
| Pages (from-to) | 1470-1478 |
| Number of pages | 9 |
| ISSN | 1061-4036 |
| DOIs | |
| Publication status | Published - Oct 2022 |
Bibliographical note
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
- ADHD, CHILDREN, DEFICIT/HYPERACTIVITY DISORDER, GENOME-WIDE ASSOCIATION, HERITABILITY, LD SCORE REGRESSION, LOCI, METAANALYSIS, PSYCHIATRIC-DISORDERS, RISK
Research areas
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