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Meta-analysis of Scandinavian Schizophrenia Exomes

View ORCID ProfileFrancesco Lescai, View ORCID ProfileJakob Grove, F. Kyle Satterstrom, View ORCID ProfileElliott Rees, View ORCID ProfileJonas Bybjerg-Grauholm, Thomas Damm Als, Jaroslaw Kalinowski, Anders Halager, View ORCID ProfileTarjinder Singh, Qibin Li, Jun Wang, James T R Walters, View ORCID ProfileMichael J Owen, View ORCID ProfileMichael C O’Donovan, View ORCID ProfileMerete Nordentoft, View ORCID ProfilePreben Bo Mortensen, View ORCID ProfileDavid M Hougaard, View ORCID ProfileThomas Werge, View ORCID ProfileOle Mors, View ORCID ProfileBenjamin M Neale, View ORCID ProfileMark J Daly, View ORCID ProfileAnders D Børglum
doi: https://doi.org/10.1101/836957
Francesco Lescai
1iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
2Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
3Center for Genomics and Personalized Medicine, Aarhus University and University Hospital, Aarhus, Denmark
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  • ORCID record for Francesco Lescai
  • For correspondence: lescai@biomed.au.dk anders@biomed.au.dk
Jakob Grove
1iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
2Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
3Center for Genomics and Personalized Medicine, Aarhus University and University Hospital, Aarhus, Denmark
4BIRC - Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark
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F. Kyle Satterstrom
5Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; 2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Elliott Rees
7MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
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Jonas Bybjerg-Grauholm
1iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
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  • ORCID record for Jonas Bybjerg-Grauholm
Thomas Damm Als
1iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
2Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
3Center for Genomics and Personalized Medicine, Aarhus University and University Hospital, Aarhus, Denmark
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Jaroslaw Kalinowski
2Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
3Center for Genomics and Personalized Medicine, Aarhus University and University Hospital, Aarhus, Denmark
4BIRC - Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark
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Anders Halager
2Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
3Center for Genomics and Personalized Medicine, Aarhus University and University Hospital, Aarhus, Denmark
4BIRC - Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark
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Tarjinder Singh
5Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; 2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Qibin Li
8BGI-Shenzhen, Shenzhen, China
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Jun Wang
8BGI-Shenzhen, Shenzhen, China
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James T R Walters
5Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; 2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Michael J Owen
7MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
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Michael C O’Donovan
7MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
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Merete Nordentoft
1iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
9Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark
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Preben Bo Mortensen
1iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
10National Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Aarhus, Denmark
11Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark
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David M Hougaard
12Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
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Thomas Werge
13Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark
14Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Ole Mors
1iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
15Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
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Benjamin M Neale
5Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; 2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Mark J Daly
5Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; 2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Anders D Børglum
1iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
2Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
3Center for Genomics and Personalized Medicine, Aarhus University and University Hospital, Aarhus, Denmark
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  • For correspondence: lescai@biomed.au.dk anders@biomed.au.dk
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Abstract

Rare genetic variants may play a prominent role in schizophrenia. We report on the to date largest whole exome sequencing study of schizophrenia case-control samples from related populations and combine with other available sequence data, analysing in total 34,084 individuals (14,302 cases). Three genes showed significant association at FDR < 0.10 (SETD1A, TAF13 and MKI67) and gene-set analyses highlighted the involvement of the synaptome and excitatory neurons, and demonstrated shared architecture with high-functioning autism.

Footnotes

  • ↵1 The iPSYCH2012 case-cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders. (2018). The iPSYCH2012 case-cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders., 23(1), 6–14. http://doi.org/10.1038/mp.2017.196

  • ↵2 Mors, O., Perto, G. P., & Mortensen, P. B. (2011). The Danish Psychiatric Central Research Register:. Scandinavian Journal of Public Health. http://doi.org/10.1177/1403494810395825

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Posted November 25, 2019.
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Meta-analysis of Scandinavian Schizophrenia Exomes
Francesco Lescai, Jakob Grove, F. Kyle Satterstrom, Elliott Rees, Jonas Bybjerg-Grauholm, Thomas Damm Als, Jaroslaw Kalinowski, Anders Halager, Tarjinder Singh, Qibin Li, Jun Wang, James T R Walters, Michael J Owen, Michael C O’Donovan, Merete Nordentoft, Preben Bo Mortensen, David M Hougaard, Thomas Werge, Ole Mors, Benjamin M Neale, Mark J Daly, Anders D Børglum
bioRxiv 836957; doi: https://doi.org/10.1101/836957
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Meta-analysis of Scandinavian Schizophrenia Exomes
Francesco Lescai, Jakob Grove, F. Kyle Satterstrom, Elliott Rees, Jonas Bybjerg-Grauholm, Thomas Damm Als, Jaroslaw Kalinowski, Anders Halager, Tarjinder Singh, Qibin Li, Jun Wang, James T R Walters, Michael J Owen, Michael C O’Donovan, Merete Nordentoft, Preben Bo Mortensen, David M Hougaard, Thomas Werge, Ole Mors, Benjamin M Neale, Mark J Daly, Anders D Børglum
bioRxiv 836957; doi: https://doi.org/10.1101/836957

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