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; J. 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

doi:10.1038/s41380-019-0559-1

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, J. 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 MortensenMerete Nordentoft, Thomas Werge, Kristin K. Nicodemus, Manuel Mattheisen, Gerome Breen, Thalia C. Eley

Research output: Contribution to journal › Article › peer-review

218 Citations (Scopus)

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_case = 25 453, n_control = 58 113) and an additional analysis of Current Anxiety Symptoms (n_case = 19 012, n_control = 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 language	English
Pages (from-to)	3292-3303
Number of pages	12
Journal	Molecular Psychiatry
Volume	25
Issue number	12
DOIs	https://doi.org/10.1038/s41380-019-0559-1
Publication status	Published - Dec 2020
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgements This research has been conducted using the UK Biobank Resource, under application 16577. This study represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). The research reported in this publication was supported by the National Institute of Mental Health of the US National Institutes of Health under Award Number U01 MH109514. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CK currently receives salary support from National Institute for Health Research (NIHR) and has previously received salary support from the Novo Nordisk UK Research Foundation, NIHR Biomedical Research Centre for Mental Health at South London and from the Maudsley National Health Service (NHS) Foundation Trust in the past. CR is supported by a grant from Fondation Peters to TE and GB. JH is supported by the National Institutes of Health grant R01 MH113665. The iPSYCH team acknowledges funding from the Lundbeck Foundation (grant no R102-A9118 and R155-2014-1724), the Novo Nordisk Foundation for supporting the Danish National Biobank resource, and grants from Aarhus and Copenhagen Universities and University Hospitals, including support to the iSEQ Center, the GenomeDK HPC facility, and the CIRRAU Center. K.L.P acknowledges funding from the Alexander von Humboldt Foundation and the Medical Research Council UK.

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.

ASJC Scopus Subject Areas

Molecular Biology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41380-019-0559-1

Cite this

Purves, K. L., Coleman, J. R. I., Meier, S. M., Rayner, C., Davis, K. A. S., Cheesman, R., Bækvad-Hansen, M., Børglum, A. D., Wan Cho, S., Jürgen Deckert, J., Gaspar, H. A., Bybjerg-Grauholm, J., Hettema, J. M., Hotopf, M., Hougaard, D., Hübel, C., Kan, C., McIntosh, A. M., Mors, O., ... Eley, T. C. (2020). A major role for common genetic variation in anxiety disorders. Molecular Psychiatry, 25(12), 3292-3303. https://doi.org/10.1038/s41380-019-0559-1

Purves, KL, Coleman, JRI, Meier, SM, Rayner, C, Davis, KAS, Cheesman, R, Bækvad-Hansen, M, Børglum, AD, Wan Cho, S, Jürgen Deckert, J, Gaspar, HA, Bybjerg-Grauholm, J, Hettema, JM, Hotopf, M, Hougaard, D, Hübel, C, Kan, C, McIntosh, AM, Mors, O, Bo Mortensen, P, Nordentoft, M, Werge, T, Nicodemus, KK, Mattheisen, M, Breen, G & Eley, TC 2020, 'A major role for common genetic variation in anxiety disorders', Molecular Psychiatry, vol. 25, no. 12, pp. 3292-3303. https://doi.org/10.1038/s41380-019-0559-1

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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 (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.",

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AU - Cheesman, Rosa

AU - Bækvad-Hansen, Marie

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AU - Jürgen Deckert, J.

AU - Gaspar, Héléna A.

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A major role for common genetic variation in anxiety disorders

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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