A major role for common genetic variation in anxiety disorders

Kirstin Purves; Jonathan Richard Iain Coleman; Sandra Melanie Meier; Christopher David Rayner; Katrina Alice Southworth Davis; Rosa Cheesman; Marie Bækvad-Hansen; Anders D Børglum; Shing Wan Choi; Juergen Deckert; Héléna Alexandra Gaspar; Jonas Bybjerg-Grauholm; John M. Hettema; Matthew Hotopf; David M. Hougaard; Christopher Huebel; Carol Kan; Andrew M. McIntosh; Ole Mors; Preben Bo Mortensen; Merete Nordentoft; Thomas Werge; Kristin K. Nicodemus; Manuel Mattheisen; Gerome Daniel Breen; Thalia Catherine Eley

doi:10.1038/s41380-019-0559-1

A major role for common genetic variation in anxiety disorders

Kirstin Purves, Jonathan Richard Iain Coleman, Sandra Melanie Meier, Christopher David Rayner, Katrina Alice Southworth Davis, Rosa Cheesman, Marie Bækvad-Hansen, Anders D Børglum, Shing Wan Choi, Juergen Deckert, Héléna Alexandra Gaspar, Jonas Bybjerg-Grauholm, John M. Hettema, Matthew Hotopf, David M. Hougaard, Christopher Huebel, Carol Kan, Andrew M. McIntosh, Ole Mors, Preben Bo MortensenMerete Nordentoft, Thomas Werge, Kristin K. Nicodemus, Manuel Mattheisen, Gerome Daniel Breen, Thalia Catherine Eley

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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 (n = 83 565) and an additional Current Anxiety Symptoms (n= 77 125) analysis. 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 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
Journal	Molecular Psychiatry
Volume	25
Issue number	12
Early online date	20 Nov 2019
DOIs	https://doi.org/10.1038/s41380-019-0559-1
Publication status	Published - 1 Dec 2020

Keywords

Anxiety
Statistical genetics
Psychiatry

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10.1038/s41380-019-0559-1

A Major Role for_PURVES_Publishedonline20Nov2019_GREEN AAMAccepted author manuscript, 138 KB

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Purves, K., Coleman, J. R. I., Meier, S. M., Rayner, C. D., Davis, K. A. S., Cheesman, R., Bækvad-Hansen, M., Børglum, A. D., Choi, S. W., Deckert, J., Gaspar, H. A., Bybjerg-Grauholm, J., Hettema, J. M., Hotopf, M., Hougaard, D. M., Huebel, 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

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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 (n = 83 565) and an additional Current Anxiety Symptoms (n= 77 125) analysis. 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 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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doi = "10.1038/s41380-019-0559-1",

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Purves, K , Coleman, JRI, Meier, SM, Rayner, CD , Davis, KAS , Cheesman, R, Bækvad-Hansen, M, Børglum, AD, Choi, SW, Deckert, J, Gaspar, HA, Bybjerg-Grauholm, J, Hettema, JM, Hotopf, M, Hougaard, DM, Huebel, C , Kan, C, McIntosh, AM, Mors, O, Mortensen, PB, Nordentoft, M, Werge, T, Nicodemus, KK, Mattheisen, M, Breen, GD & 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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T1 - A major role for common genetic variation in anxiety disorders

AU - Purves, Kirstin

AU - Coleman, Jonathan Richard Iain

AU - Meier, Sandra Melanie

AU - Rayner, Christopher David

AU - Davis, Katrina Alice Southworth

AU - Cheesman, Rosa

AU - Bækvad-Hansen, Marie

AU - Børglum, Anders D

AU - Choi, Shing Wan

AU - Deckert, Juergen

AU - Gaspar, Héléna Alexandra

AU - Bybjerg-Grauholm, Jonas

AU - Hettema, John M.

AU - Hotopf, Matthew

AU - Hougaard, David M.

AU - Huebel, Christopher

AU - Kan, Carol

AU - McIntosh, Andrew M.

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - Nicodemus, Kristin K.

AU - Mattheisen, Manuel

AU - Breen, Gerome Daniel

AU - Eley, Thalia Catherine

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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 = 83 565) and an additional Current Anxiety Symptoms (n= 77 125) analysis. 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 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.

AB - 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 = 83 565) and an additional Current Anxiety Symptoms (n= 77 125) analysis. 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 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.

KW - Anxiety

KW - Statistical genetics

KW - Psychiatry

UR - https://www.biorxiv.org/content/10.1101/203844v1

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DO - 10.1038/s41380-019-0559-1

M3 - Article

SN - 1359-4184

VL - 25

SP - 3292

EP - 3303

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 12

ER -

A major role for common genetic variation in anxiety disorders

Abstract

Keywords

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Genetic Variants Associated With Anxiety and Stress-Related Disorders A Genome-Wide Association Study and Mouse-Model Study

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