An official website of the United States government
The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before
sharing sensitive information, make sure you’re on a federal
government site.
The site is secure.
The https:// ensures that you are connecting to the
official website and that any information you provide is encrypted
and transmitted securely.
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. [email protected].
23 NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. [email protected].
24 King's College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, London, UK. [email protected].
25 NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. [email protected].
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. [email protected].
23 NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. [email protected].
24 King's College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, London, UK. [email protected].
25 NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. [email protected].
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.
Figure 1.. Manhattan and Q-Q plots for UK Biobank anxiety analyses
Manhattan and Q-Q plots…
Figure 1.. Manhattan and Q-Q plots for UK Biobank anxiety analyses
Manhattan and Q-Q plots of p-values of Single Nucleotide Polymorphisms (SNP) based association analyses of anxiety in the UK Biobank. In the Manhattan plots, the threshold for genome-wide significance (p −08) Is indicated by the red line, while the blue line indicates the threshold for suggestive significance (p < 1×10−5). Top panel showing results for our core Lifetime Anxiety Disorder analysis. Bottom panel showing results for the Current Anxiety Symptoms analysis.
Figure 2.. Genetic correlations between UK Biobank…
Figure 2.. Genetic correlations between UK Biobank Lifetime Anxiety Disorder and significantly associated external traits
Figure 2.. Genetic correlations between UK Biobank Lifetime Anxiety Disorder and significantly associated external traits
Figure showing genetic correlations (rG) between UK Biobank “Lifetime Anxiety Disorder” and external phenotypes generated from LDhub. Only traits where correlation exceeded Bonferroni corrected threshold of p < 0.0002 shown here. Depression and neuroticism were not included in this analysis as they have been included as replication samples in subsequent analyses. See supplementary table 7 for rG with the latest publically available neuroticism and MDD GWAS samples including UK Biobank. Asterisks (*) Indicates source study sample wholly or partially included UK Biobank participants. Correlations ordered first by rG within category. Bars show standard error of the estimate.
Figure 3.. Gene Manhattan plot with top…
Figure 3.. Gene Manhattan plot with top significant gene per chromosome
Manhattan plots of p-values…
Figure 3.. Gene Manhattan plot with top significant gene per chromosome
Manhattan plots of p-values of gene-wise association analyses of “Lifetime Anxiety Disorder” in the UK Biobank. In the Manhattan plots, the threshold for gene-wide significance (p
Figure 4.. Manhattan and Q-Q plots for…
Figure 4.. Manhattan and Q-Q plots for meta-analysis of all Lifetime Anxiety Disorder samples
Manhattan…
Figure 4.. Manhattan and Q-Q plots for meta-analysis of all Lifetime Anxiety Disorder samples
Manhattan and Q-Q plots of p-values of Single Nucleotide Polymorphisms (SNP) based association analyses of combined sample meta-analysis across three Lifetime Anxiety Disorder cohorts (UK Biobank, ANGST and iPSYCH). In the Manhattan plots, the threshold for genome-wide significance (p
Stein MB, Chen CY, Jain S, Jensen KP, He F, Heeringa SG, Kessler RC, Maihofer A, Nock MK, Ripke S, Sun X, Thomas ML, Ursano RJ, Smoller JW, Gelernter J; Army STARRS Collaborators.Stein MB, et al.Am J Med Genet B Neuropsychiatr Genet. 2017 Mar;174(2):120-131. doi: 10.1002/ajmg.b.32520.Am J Med Genet B Neuropsychiatr Genet. 2017.Corrected and republished in: Am J Med Genet B Neuropsychiatr Genet. 2017 Jun;174(4):470-482. doi: 10.1002/ajmg.b.32541.PMID: 28224735Free PMC article.Corrected and republished.
Kessler RC, Aguilar-Gaxiola S, Alonso J, Chatterji S, Lee S, Ormel J et al. The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiol Psichiatr Soc 2009; 18: 23–33.
-
PMC
-
PubMed
Wittchen H-U, Jacobi F. Size and burden of mental disorders in Europe--a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 2005; 15: 357–376.
-
PubMed
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1789–1858.
-
PMC
-
PubMed
Polderman TJC, Benyamin B, de Leeuw CA, Sullivan PF, van Bochoven A, Visscher PM et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet 2015; 47: 702–709.
-
PubMed
