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Genome-wide association study of school grades identifies a genetic overlap between language ability, psychopathology and creativity

View ORCID ProfileVeera M. Rajagopal, View ORCID ProfileAndrea Ganna, View ORCID ProfileJonathan R. I. Coleman, Andrea G. Allegrini, View ORCID ProfileGeorgios Voloudakis, View ORCID ProfileJakob Grove, View ORCID ProfileThomas D. Als, View ORCID ProfileHenriette T. Horsdal, View ORCID ProfileLiselotte Petersen, View ORCID ProfileVivek Appadurai, View ORCID ProfileAndrew Schork, View ORCID ProfileAlfonso Buil, View ORCID ProfileCynthia M. Bulik, View ORCID ProfileJonas Bybjerg-Grauholm, Marie Bækvad-Hansen, View ORCID ProfileDavid M. Hougaard, View ORCID ProfileOle Mors, View ORCID ProfileMerete Nordentoft, View ORCID ProfileThomas Werge, iPSYCH-Broad Consortium, View ORCID ProfilePreben Bo Mortensen, View ORCID ProfileGerome Breen, Panos Roussos, View ORCID ProfileRobert Plomin, View ORCID ProfileEsben Agerbo, View ORCID ProfileAnders D. Børglum, View ORCID ProfileDitte Demontis
doi: https://doi.org/10.1101/2020.05.09.075226
Veera M. Rajagopal
1Department of Biomedicine, Aarhus University, Aarhus, Denmark
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
3Center for Genome Analysis and Personalized Medicine, Aarhus, Denmark
4Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
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  • For correspondence: veera@biomed.au.dk ditte@biomed.au.dk
Andrea Ganna
5Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
6Analytic and Translational Genetics unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA
7Broad Institute, Cambridge, USA
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Jonathan R. I. Coleman
8Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK
9National Institute of Health Research Maudsley Biomedical Research Centre, South London and Maudsley National Health Service Trust, London, UK
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Andrea G. Allegrini
8Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK
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Georgios Voloudakis
10Department of Psychiatry, Pamela Sklar Division of Psychiatric Genomics and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
11James J. Peters VA Medical Center, Bronx, NY, USA
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Jakob Grove
1Department of Biomedicine, Aarhus University, Aarhus, Denmark
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
3Center for Genome Analysis and Personalized Medicine, Aarhus, Denmark
4Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
12Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark
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Thomas D. Als
1Department of Biomedicine, Aarhus University, Aarhus, Denmark
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
3Center for Genome Analysis and Personalized Medicine, Aarhus, Denmark
4Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
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Henriette T. Horsdal
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
13The National Centre for Register-based Research (NCRR), Aarhus University, Aarhus, Denmark
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Liselotte Petersen
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
13The National Centre for Register-based Research (NCRR), Aarhus University, Aarhus, Denmark
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Vivek Appadurai
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
14Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, DK
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Andrew Schork
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
14Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, DK
15Neurogenomics Division, The Translational Genomics Research Institute (TGEN), Phoenix, AZ, USA
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Alfonso Buil
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
14Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, DK
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Cynthia M. Bulik
16Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, USA
17Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
18Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, USA
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Jonas Bybjerg-Grauholm
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
19Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
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Marie Bækvad-Hansen
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
19Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
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David M. Hougaard
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
19Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
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Ole Mors
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
20Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Aarhus, Denmark
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Merete Nordentoft
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
21Mental Health Center Copenhagen, Mental Health Services in The CapitalRegion of Denmark
22Dept. Clinical Medicine, Faculty of Health Science, University of Copenhagen
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Thomas Werge
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
14Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, DK
22Dept. Clinical Medicine, Faculty of Health Science, University of Copenhagen
23Center for GeoGenetics, GLOBE Institute, University of Copenhagen, Denmark
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2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
7Broad Institute, Cambridge, USA
Preben Bo Mortensen
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
4Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
13The National Centre for Register-based Research (NCRR), Aarhus University, Aarhus, Denmark
24Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Aarhus, Denmark
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Gerome Breen
8Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK
9National Institute of Health Research Maudsley Biomedical Research Centre, South London and Maudsley National Health Service Trust, London, UK
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Panos Roussos
10Department of Psychiatry, Pamela Sklar Division of Psychiatric Genomics and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
11James J. Peters VA Medical Center, Bronx, NY, USA
25Department of Genetics and Genomic Sciences and Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Robert Plomin
8Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK
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Esben Agerbo
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
4Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
13The National Centre for Register-based Research (NCRR), Aarhus University, Aarhus, Denmark
24Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Aarhus, Denmark
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Anders D. Børglum
1Department of Biomedicine, Aarhus University, Aarhus, Denmark
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
3Center for Genome Analysis and Personalized Medicine, Aarhus, Denmark
4Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
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Ditte Demontis
1Department of Biomedicine, Aarhus University, Aarhus, Denmark
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
3Center for Genome Analysis and Personalized Medicine, Aarhus, Denmark
4Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
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  • For correspondence: veera@biomed.au.dk ditte@biomed.au.dk
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Abstract

Individuals with psychiatric disorders perform differently in school compared to the general population. Genetic factors contribute substantially to such differences. It is however unclear if differential performance is seen across all cognitive domains such as math and language. Here we report a genome-wide association study (GWAS) of school grades in 30,982 individuals (18,495 with and 12,487 without one or more of six major psychiatric disorders) and a replication study in 4,547 individuals. GWAS of overall school performance yielded results that were highly similar to the results of a previous GWAS of educational attainment. Analyzing subject specific grades, we observed that math performance was severely affected whereas language performance (Danish and English) was relatively unaffected or enhanced in those with psychiatric disorders compared to controls. We found that the genetic variants associated with poor math performance, but better language performance were also associated with increased risk for multiple psychiatric disorders. The same variants were also associated with creativity, which we show through a polygenic score analysis of 2953 creative professionals and 164,622 controls. The results overall suggest that risk for psychiatric disorders, language ability and creativity might have overlapping genetic roots.

Competing Interest Statement

CM Bulik reports: Shire (grant recipient, Scientific Advisory Board member); Idorsia (consultant); Pearson (author, royalty recipient).

Footnotes

  • One of the author names was missed during the first upload. It's now corrected.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Genome-wide association study of school grades identifies a genetic overlap between language ability, psychopathology and creativity
Veera M. Rajagopal, Andrea Ganna, Jonathan R. I. Coleman, Andrea G. Allegrini, Georgios Voloudakis, Jakob Grove, Thomas D. Als, Henriette T. Horsdal, Liselotte Petersen, Vivek Appadurai, Andrew Schork, Alfonso Buil, Cynthia M. Bulik, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, David M. Hougaard, Ole Mors, Merete Nordentoft, Thomas Werge, iPSYCH-Broad Consortium, Preben Bo Mortensen, Gerome Breen, Panos Roussos, Robert Plomin, Esben Agerbo, Anders D. Børglum, Ditte Demontis
bioRxiv 2020.05.09.075226; doi: https://doi.org/10.1101/2020.05.09.075226
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Genome-wide association study of school grades identifies a genetic overlap between language ability, psychopathology and creativity
Veera M. Rajagopal, Andrea Ganna, Jonathan R. I. Coleman, Andrea G. Allegrini, Georgios Voloudakis, Jakob Grove, Thomas D. Als, Henriette T. Horsdal, Liselotte Petersen, Vivek Appadurai, Andrew Schork, Alfonso Buil, Cynthia M. Bulik, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, David M. Hougaard, Ole Mors, Merete Nordentoft, Thomas Werge, iPSYCH-Broad Consortium, Preben Bo Mortensen, Gerome Breen, Panos Roussos, Robert Plomin, Esben Agerbo, Anders D. Børglum, Ditte Demontis
bioRxiv 2020.05.09.075226; doi: https://doi.org/10.1101/2020.05.09.075226

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