A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders

Christopher Rayner; Jonathan R.I. Coleman; Kirstin L. Purves; John Hodsoll; Kimberley Goldsmith; Georg W. Alpers; Evelyn Andersson; Volker Arolt; Julia Boberg; Susan Bögels; Cathy Creswell; Peter Cooper; Charles Curtis; Jürgen Deckert; Katharina Domschke; Samir El Alaoui; Lydia Fehm; Thomas Fydrich; Alexander L. Gerlach; Anja Grocholewski; Kurt Hahlweg; Alfons Hamm; Erik Hedman; Einar R. Heiervang; Jennifer L. Hudson; Peter Jöhren; Robert Keers; Tilo Kircher; Thomas Lang; Catharina Lavebratt; Sang-hyuck Lee; Kathryn J. Lester; Nils Lindefors; Jürgen Margraf; Maaike Nauta; Christiane A. Pané-Farré; Paul Pauli; Ronald M. Rapee; Andreas Reif; Winfried Rief; Susanna Roberts; Martin Schalling; Silvia Schneider; Wendy K. Silverman; Andreas Ströhle; Tobias Teismann; Mikael Thastum; Andre Wannemüller; Heike Weber; Hans Ulrich Wittchen; Christiane Wolf; Christian Rück; Gerome Breen; Thalia C. Eley

doi:10.1038/s41398-019-0481-y

A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders

Christopher Rayner, Jonathan R.I. Coleman, Kirstin L. Purves, John Hodsoll, Kimberley Goldsmith, Georg W. Alpers, Evelyn Andersson, Volker Arolt, Julia Boberg, Susan Bögels, Cathy Creswell, Peter Cooper, Charles Curtis, Jürgen Deckert, Katharina Domschke, Samir El Alaoui, Lydia Fehm, Thomas Fydrich, Alexander L. Gerlach, Anja GrocholewskiKurt Hahlweg, Alfons Hamm, Erik Hedman, Einar R. Heiervang, Jennifer L. Hudson, Peter Jöhren, Robert Keers, Tilo Kircher, Thomas Lang, Catharina Lavebratt, Sang-hyuck Lee, Kathryn J. Lester, Nils Lindefors, Jürgen Margraf, Maaike Nauta, Christiane A. Pané-Farré, Paul Pauli, Ronald M. Rapee, Andreas Reif, Winfried Rief, Susanna Roberts, Martin Schalling, Silvia Schneider, Wendy K. Silverman, Andreas Ströhle, Tobias Teismann, Mikael Thastum, Andre Wannemüller, Heike Weber, Hans Ulrich Wittchen, Christiane Wolf, Christian Rück, Gerome Breen^*, Thalia C. Eley

^*Corresponding author for this work

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Abstract

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r_g ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h²_SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h²_SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.

Original language	English
Article number	150
Pages (from-to)	1-13
Number of pages	13
Journal	Translational Psychiatry
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41398-019-0481-y
Publication status	Published - 23 May 2019

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Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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Rayner, C., Coleman, J. R. I., Purves, K. L., Hodsoll, J., Goldsmith, K., Alpers, G. W., Andersson, E., Arolt, V., Boberg, J., Bögels, S., Creswell, C., Cooper, P., Curtis, C., Deckert, J., Domschke, K., El Alaoui, S., Fehm, L., Fydrich, T., Gerlach, A. L., ... Eley, T. C. (2019). A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders. Translational Psychiatry, 9(1), 1-13. Article 150. https://doi.org/10.1038/s41398-019-0481-y

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title = "A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders",

abstract = "Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.",

author = "Christopher Rayner and Coleman, {Jonathan R.I.} and Purves, {Kirstin L.} and John Hodsoll and Kimberley Goldsmith and Alpers, {Georg W.} and Evelyn Andersson and Volker Arolt and Julia Boberg and Susan B{\"o}gels and Cathy Creswell and Peter Cooper and Charles Curtis and J{\"u}rgen Deckert and Katharina Domschke and {El Alaoui}, Samir and Lydia Fehm and Thomas Fydrich and Gerlach, {Alexander L.} and Anja Grocholewski and Kurt Hahlweg and Alfons Hamm and Erik Hedman and Heiervang, {Einar R.} and Hudson, {Jennifer L.} and Peter J{\"o}hren and Robert Keers and Tilo Kircher and Thomas Lang and Catharina Lavebratt and Sang-hyuck Lee and Lester, {Kathryn J.} and Nils Lindefors and J{\"u}rgen Margraf and Maaike Nauta and Pan{\'e}-Farr{\'e}, {Christiane A.} and Paul Pauli and Rapee, {Ronald M.} and Andreas Reif and Winfried Rief and Susanna Roberts and Martin Schalling and Silvia Schneider and Silverman, {Wendy K.} and Andreas Str{\"o}hle and Tobias Teismann and Mikael Thastum and Andre Wannem{\"u}ller and Heike Weber and Wittchen, {Hans Ulrich} and Christiane Wolf and Christian R{\"u}ck and Gerome Breen and Eley, {Thalia C.}",

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Rayner, C, Coleman, JRI, Purves, KL, Hodsoll, J, Goldsmith, K, Alpers, GW, Andersson, E, Arolt, V, Boberg, J, Bögels, S, Creswell, C, Cooper, P, Curtis, C, Deckert, J, Domschke, K, El Alaoui, S, Fehm, L, Fydrich, T, Gerlach, AL, Grocholewski, A, Hahlweg, K, Hamm, A, Hedman, E, Heiervang, ER, Hudson, JL, Jöhren, P, Keers, R, Kircher, T, Lang, T, Lavebratt, C, Lee, S, Lester, KJ, Lindefors, N, Margraf, J, Nauta, M, Pané-Farré, CA, Pauli, P, Rapee, RM, Reif, A, Rief, W, Roberts, S, Schalling, M, Schneider, S, Silverman, WK, Ströhle, A, Teismann, T, Thastum, M, Wannemüller, A, Weber, H, Wittchen, HU, Wolf, C, Rück, C, Breen, G & Eley, TC 2019, 'A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders', Translational Psychiatry, vol. 9, no. 1, 150, pp. 1-13. https://doi.org/10.1038/s41398-019-0481-y

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T1 - A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders

AU - Rayner, Christopher

AU - Coleman, Jonathan R.I.

AU - Purves, Kirstin L.

AU - Hodsoll, John

AU - Goldsmith, Kimberley

AU - Alpers, Georg W.

AU - Andersson, Evelyn

AU - Arolt, Volker

AU - Boberg, Julia

AU - Bögels, Susan

AU - Creswell, Cathy

AU - Cooper, Peter

AU - Curtis, Charles

AU - Deckert, Jürgen

AU - Domschke, Katharina

AU - El Alaoui, Samir

AU - Fehm, Lydia

AU - Fydrich, Thomas

AU - Gerlach, Alexander L.

AU - Grocholewski, Anja

AU - Hahlweg, Kurt

AU - Hamm, Alfons

AU - Hedman, Erik

AU - Heiervang, Einar R.

AU - Hudson, Jennifer L.

AU - Jöhren, Peter

AU - Keers, Robert

AU - Kircher, Tilo

AU - Lang, Thomas

AU - Lavebratt, Catharina

AU - Lee, Sang-hyuck

AU - Lester, Kathryn J.

AU - Lindefors, Nils

AU - Margraf, Jürgen

AU - Nauta, Maaike

AU - Pané-Farré, Christiane A.

AU - Pauli, Paul

AU - Rapee, Ronald M.

AU - Reif, Andreas

AU - Rief, Winfried

AU - Roberts, Susanna

AU - Schalling, Martin

AU - Schneider, Silvia

AU - Silverman, Wendy K.

AU - Ströhle, Andreas

AU - Teismann, Tobias

AU - Thastum, Mikael

AU - Wannemüller, Andre

AU - Weber, Heike

AU - Wittchen, Hans Ulrich

AU - Wolf, Christiane

AU - Rück, Christian

AU - Breen, Gerome

AU - Eley, Thalia C.

N1 - Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2019/5/23

Y1 - 2019/5/23

N2 - Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.

AB - Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.

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A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders

Abstract

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A stepped care approach for the management of childhood anxiety disorders: A randomised controlled trial

Environmental and genetic risk factors for anxiety disorders in children

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A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders

Abstract

Bibliographical note

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Other files and links

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A stepped care approach for the management of childhood anxiety disorders: A randomised controlled trial

Environmental and genetic risk factors for anxiety disorders in children

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