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Mol Psychiatry. 2019 Nov 20. doi: 10.1038/s41380-019-0559-1. [Epub ahead of print]

A major role for common genetic variation in anxiety disorders.

Author information

1
King's College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, London, UK.
2
NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK.
3
Child and Adolescent Mental Health Centre-Mental Health Services Capital Region, Copenhagen Region, Denmark.
4
Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
5
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
6
King's College London; Institute of Psychiatry, Psychology & Neuroscience, London, UK.
7
Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
8
Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
9
Centre for integrative Sequencing (iSEQ), Aarhus University, Aarhus C, Denmark.
10
Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany.
11
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
12
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
13
King's College London; Psychological Medicine; Institute of Psychiatry, Psychology & Neuroscience, London, UK.
14
Division of Psychiatry, Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.
15
MRC Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK.
16
National Centre for Register-Based Research, Aarhus University, Aarhus C, Denmark.
17
Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
18
Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.
19
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
20
Centre for Genomic and Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK.
21
Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
22
King's College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, London, UK. gerome.breen@kcl.ac.uk.
23
NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. gerome.breen@kcl.ac.uk.
24
King's College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, London, UK. thalia.eley@kcl.ac.uk.
25
NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. thalia.eley@kcl.ac.uk.

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 (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.

PMID:
31748690
DOI:
10.1038/s41380-019-0559-1

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