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Preben Bo Mortensen

A major role for common genetic variation in anxiety disorders

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  • Kirstin L Purves, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
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  • Jonathan R I Coleman, South London and Maudsley NHS Trust, NIHR Biomedical Research Centre for Mental Health, London, UK. gerome.breen@kcl.ac.uk.
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  • Sandra M Meier
  • Christopher Rayner, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
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  • Katrina A S Davis, Department of Child and Adolescent Psychiatry, Institute of Psychiatry Psychology and Neuroscience, King's College, London, London.
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  • Rosa Cheesman, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
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  • Marie Bækvad-Hansen, Danish Centre for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
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  • Anders D Børglum
  • Shing Wan Cho, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
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  • J Jürgen Deckert, Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
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  • Héléna A Gaspar, South London and Maudsley NHS Trust, NIHR Biomedical Research Centre for Mental Health, London, UK. gerome.breen@kcl.ac.uk.
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  • Jonas Bybjerg-Grauholm, Danish Centre for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
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  • John M Hettema, Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
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  • Matthew Hotopf, Department of Child and Adolescent Psychiatry, Institute of Psychiatry Psychology and Neuroscience, King's College, London, London.
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  • David Hougaard, Danish Centre for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
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  • Christopher Hübel, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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  • Carol Kan, From the *National Centre for Register-based Research; †CRESTAR, Aarhus University, Aarhus, Denmark; ‡Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark; §Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff; ∥Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom; ¶Centre for Integrated Register-Based Research at Aarhus University (CIRRAU); and #iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
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  • Andrew M McIntosh, MRC Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK.
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  • Ole Mors
  • Preben Bo Mortensen
  • Merete Nordentoft, Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. karkoe@rm.dk.
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  • Thomas Werge, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark Danish Arrhythmia Research Centre, University of Copenhagen, Copenhagen, Denmark.
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  • Kristin K Nicodemus, Centre 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
  • Gerome Breen, South London and Maudsley NHS Trust, NIHR Biomedical Research Centre for Mental Health, London, UK. gerome.breen@kcl.ac.uk.
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  • Thalia C Eley, South London and Maudsley NHS Trust, NIHR Biomedical Research Centre for Mental Health, London, UK. thalia.eley@kcl.ac.uk.

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (ncase = 25 453, ncontrol = 58 113) and an additional analysis of Current Anxiety Symptoms (ncase = 19 012, ncontrol = 58 113). 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 positive 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.

OriginalsprogEngelsk
TidsskriftMolecular Psychiatry
ISSN1359-4184
DOI
StatusE-pub ahead of print - 2020

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