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A Major Role for Common Genetic Variation in Anxiety Disorders

View ORCID ProfileKirstin L. Purves, View ORCID ProfileJonathan R. I. Coleman, Sandra M. Meier, View ORCID ProfileChristopher Rayner, Katrina A. S. Davis, View ORCID ProfileRosa Cheesman, Marie Bækvad-Hansen, Anders D. Børglum, View ORCID ProfileShing Wan Cho, Jürgen Deckert, Héléna A. Gaspar, Jonas Bybjerg-Grauholm, View ORCID ProfileJohn M. Hettema, Matthew Hotopf, David Hougaard, Christopher Hübel, Carol Kan, View ORCID ProfileAndrew M. McIntosh, Ole Mors, Preben Bo Mortensen, Merete Nordentoft, Thomas Werge, View ORCID ProfileKristin K. Nicodemus, Manuel Mattheisen, View ORCID ProfileGerome Breen, View ORCID ProfileThalia C. Eley
doi: https://doi.org/10.1101/203844
Kirstin L. Purves
1King’s College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience; London, UK
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Jonathan R. I. Coleman
1King’s College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience; London, UK
2NIHR Biomedical Research Centre; South London and Maudsley NHS Trust; London, UK
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Sandra M. Meier
3Child and Adolescent Mental Health Centre–Mental Health Services Capital Region; Copenhagen Region; Denmark
4Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
5The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
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Christopher Rayner
1King’s College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience; London, UK
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Katrina A. S. Davis
2NIHR Biomedical Research Centre; South London and Maudsley NHS Trust; London, UK
6King’s College London; Institute of Psychiatry, Psychology & Neuroscience; London, UK
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Rosa Cheesman
1King’s College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience; London, UK
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Marie Bækvad-Hansen
5The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
7Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
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Anders D. Børglum
5The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
8Department of Biomedicine, Aarhus University, Aarhus C, Denmark
9Centre for integrative Sequencing (iSEQ), Aarhus University, Aarhus C, Denmark
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Shing Wan Cho
1King’s College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience; London, UK
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Jürgen Deckert
10Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany
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Héléna A. Gaspar
1King’s College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience; London, UK
2NIHR Biomedical Research Centre; South London and Maudsley NHS Trust; London, UK
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Jonas Bybjerg-Grauholm
5The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
7Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
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John M. Hettema
11Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA
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Matthew Hotopf
2NIHR Biomedical Research Centre; South London and Maudsley NHS Trust; London, UK
6King’s College London; Institute of Psychiatry, Psychology & Neuroscience; London, UK
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David Hougaard
5The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
7Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
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Christopher Hübel
1King’s College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience; London, UK
2NIHR Biomedical Research Centre; South London and Maudsley NHS Trust; London, UK
12Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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Carol Kan
13King’s College London; Psychological Medicine; Institute of Psychiatry, Psychology & Neuroscience; London, UK
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Andrew M. McIntosh
14Division of Psychiatry, Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK
15MRC Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK
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Ole Mors
4Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
5The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
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Preben Bo Mortensen
5The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
9Centre for integrative Sequencing (iSEQ), Aarhus University, Aarhus C, Denmark
16National Centre for Register-Based Research, Aarhus University, Aarhus C, Denmark
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Merete Nordentoft
5The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
17Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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Thomas Werge
5The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
18Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark
19Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Kristin K. Nicodemus
20Centre for Genomic and Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK
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Manuel Mattheisen
5The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
8Department of Biomedicine, Aarhus University, Aarhus C, Denmark
10Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany
21Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden
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Gerome Breen
1King’s College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience; London, UK
2NIHR Biomedical Research Centre; South London and Maudsley NHS Trust; London, UK
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  • For correspondence: gerome.breen@kcl.ac.uk thalia.eley@kcl.ac.uk
Thalia C. Eley
1King’s College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience; London, UK
2NIHR Biomedical Research Centre; South London and Maudsley NHS Trust; London, UK
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  • For correspondence: gerome.breen@kcl.ac.uk thalia.eley@kcl.ac.uk
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Abstract

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (n = 83 565) and an additional Current Anxiety Symptoms (n= 77 125) analysis. The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%. Five novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism, and a locus overlapping the BDNF receptor gene, NTRK2. Anxiety showed significant genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies. We conclude that common genetic variation accounts for a substantive proportion of the genetic architecture underlying anxiety.

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A Major Role for Common Genetic Variation in Anxiety Disorders
Kirstin L. Purves, Jonathan R. I. Coleman, Sandra M. Meier, Christopher Rayner, Katrina A. S. Davis, Rosa Cheesman, Marie Bækvad-Hansen, Anders D. Børglum, Shing Wan Cho, Jürgen Deckert, Héléna A. Gaspar, Jonas Bybjerg-Grauholm, John M. Hettema, Matthew Hotopf, David Hougaard, Christopher Hübel, Carol Kan, Andrew M. McIntosh, Ole Mors, Preben Bo Mortensen, Merete Nordentoft, Thomas Werge, Kristin K. Nicodemus, Manuel Mattheisen, Gerome Breen, Thalia C. Eley
bioRxiv 203844; doi: https://doi.org/10.1101/203844
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A Major Role for Common Genetic Variation in Anxiety Disorders
Kirstin L. Purves, Jonathan R. I. Coleman, Sandra M. Meier, Christopher Rayner, Katrina A. S. Davis, Rosa Cheesman, Marie Bækvad-Hansen, Anders D. Børglum, Shing Wan Cho, Jürgen Deckert, Héléna A. Gaspar, Jonas Bybjerg-Grauholm, John M. Hettema, Matthew Hotopf, David Hougaard, Christopher Hübel, Carol Kan, Andrew M. McIntosh, Ole Mors, Preben Bo Mortensen, Merete Nordentoft, Thomas Werge, Kristin K. Nicodemus, Manuel Mattheisen, Gerome Breen, Thalia C. Eley
bioRxiv 203844; doi: https://doi.org/10.1101/203844

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