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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, King’s College London, NIHR Biomedical Research Centre
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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., NIHR Biomedical Research Centre
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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, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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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, King’s College London, NIHR Biomedical Research Centre
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  • Jonas Bybjerg-Grauholm, Danish Centre for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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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., NIHR Biomedical Research Centre
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  • David Hougaard, Danish Centre for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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  • Christopher Hübel, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., NIHR Biomedical Research Centre, King’s College London
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  • Carol Kan, King’s College London
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  • Andrew M McIntosh, MRC Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK., The University of Edinburgh
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  • Ole Mors
  • Preben Bo Mortensen
  • Merete Nordentoft, University of Copenhagen, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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  • Thomas Werge, University of Copenhagen, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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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, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Karolinska Institutet, University of Würzburg
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  • Gerome Breen, King’s College London, NIHR Biomedical Research Centre
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  • Thalia C Eley, King’s College London, NIHR Biomedical Research Centre

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.

Original languageEnglish
JournalMolecular Psychiatry
Volume25
Pages (from-to)3292-3303
Number of pages12
ISSN1359-4184
DOIs
Publication statusPublished - Dec 2020

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