A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Xueyi Shen; David M. Howard; Mark J. Adams; W. David Hill; Toni Kim Clarke; Mark J. Adams; Toni Kim Clarke; Andrew M. McIntosh; Ian J. Deary; Naomi R. Wray; Stephan Ripke; Manuel Mattheisen; Maciej Trzaskowski; Enda M. Byrne; Abdel Abdellaoui; Esben Agerbo; Tracy M. Air; Till F.M. Andlauer; Silviu Alin Bacanu; Marie Bækvad-Hansen; Aartjan T.F. Beekman; Tim B. Bigdeli; Elisabeth B. Binder; Julien Bryois; Henriette N. Buttenschøn; Jonas Bybjerg-Grauholm; Na Cai; Enrique Castelao; Jane Hvarregaard Christensen; Jonathan R.I. Coleman; Lucía Colodro-Conde; Baptiste Couvy-Duchesne; Nick Craddock; Gregory E. Crawford; Gail Davies; Franziska Degenhardt; Eske M. Derks; Nese Direk; Conor V. Dolan; Erin C. Dunn; Thalia C. Eley; Valentina Escott-Price; Farnush Farhadi Hassan Kiadeh; Hilary K. Finucane; Jerome C. Foo; Thomas F. Hansen; Wesley Thompson; Shantel Marie Weinsheimer; Merete Nordentoft; Thomas Werge; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1038/s41467-020-16022-0

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Xueyi Shen, David M. Howard, Mark J. Adams, W. David Hill, Toni Kim Clarke, Mark J. Adams, Toni Kim Clarke, Andrew M. McIntosh, Ian J. Deary, Naomi R. Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Esben Agerbo, Tracy M. Air, Till F.M. Andlauer, Silviu Alin Bacanu, Marie Bækvad-HansenAartjan T.F. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Jonathan R.I. Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Franziska Degenhardt, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Thomas F. Hansen, Wesley Thompson, Shantel Marie Weinsheimer, Merete Nordentoft, Thomas Werge, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

86 Citationer (Scopus)

Abstract

Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, p FDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, p FDR: 0.049 to 1.28 × 10 -14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.

Originalsprog	Engelsk
Tidsskrift	Nature Communications
Vol/bind	11
Udgave nummer	1
Sider (fra-til)	2301
ISSN	2041-1722
DOI	https://doi.org/10.1038/s41467-020-16022-0
Status	Udgivet - 8 maj 2020

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Shen, X., Howard, D. M., Adams, M. J., Hill, W. D., Clarke, T. K., Adams, M. J., Clarke, T. K., McIntosh, A. M., Deary, I. J., Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Agerbo, E., Air, T. M., Andlauer, T. F. M., Bacanu, S. A., ... Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2020). A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank. Nature Communications, 11(1), 2301. https://doi.org/10.1038/s41467-020-16022-0

Shen, X, Howard, DM, Adams, MJ, Hill, WD, Clarke, TK, Adams, MJ, Clarke, TK, McIntosh, AM, Deary, IJ, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, SA, Bækvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Bryois, J, Buttenschøn, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Coleman, JRI, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Hansen, TF , Thompson, W, Weinsheimer, SM, Nordentoft, M , Werge, T & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2020, 'A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank', Nature Communications, bind 11, nr. 1, s. 2301. https://doi.org/10.1038/s41467-020-16022-0

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abstract = "Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, p FDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, p FDR: 0.049 to 1.28 × 10 -14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression. ",

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author = "Xueyi Shen and Howard, {David M.} and Adams, {Mark J.} and Hill, {W. David} and Clarke, {Toni Kim} and Adams, {Mark J.} and Clarke, {Toni Kim} and McIntosh, {Andrew M.} and Deary, {Ian J.} and Wray, {Naomi R.} and Stephan Ripke and Manuel Mattheisen and Maciej Trzaskowski and Byrne, {Enda M.} and Abdel Abdellaoui and Esben Agerbo and Air, {Tracy M.} and Andlauer, {Till F.M.} and Bacanu, {Silviu Alin} and Marie B{\ae}kvad-Hansen and Beekman, {Aartjan T.F.} and Bigdeli, {Tim B.} and Binder, {Elisabeth B.} and Julien Bryois and Buttensch{\o}n, {Henriette N.} and Jonas Bybjerg-Grauholm and Na Cai and Enrique Castelao and Christensen, {Jane Hvarregaard} and Coleman, {Jonathan R.I.} and Luc{\'i}a Colodro-Conde and Baptiste Couvy-Duchesne and Nick Craddock and Crawford, {Gregory E.} and Gail Davies and Franziska Degenhardt and Derks, {Eske M.} and Nese Direk and Dolan, {Conor V.} and Dunn, {Erin C.} and Eley, {Thalia C.} and Valentina Escott-Price and Kiadeh, {Farnush Farhadi Hassan} and Finucane, {Hilary K.} and Foo, {Jerome C.} and Hansen, {Thomas F.} and Wesley Thompson and Weinsheimer, {Shantel Marie} and Merete Nordentoft and Thomas Werge and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",

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AU - Shen, Xueyi

AU - Howard, David M.

AU - Adams, Mark J.

AU - Hill, W. David

AU - Clarke, Toni Kim

AU - Adams, Mark J.

AU - Clarke, Toni Kim

AU - McIntosh, Andrew M.

AU - Deary, Ian J.

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till F.M.

AU - Bacanu, Silviu Alin

AU - Bækvad-Hansen, Marie

AU - Beekman, Aartjan T.F.

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AU - Coleman, Jonathan R.I.

AU - Colodro-Conde, Lucía

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Davies, Gail

AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - Direk, Nese

AU - Dolan, Conor V.

AU - Dunn, Erin C.

AU - Eley, Thalia C.

AU - Escott-Price, Valentina

AU - Kiadeh, Farnush Farhadi Hassan

AU - Finucane, Hilary K.

AU - Foo, Jerome C.

AU - Hansen, Thomas F.

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N2 - Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, p FDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, p FDR: 0.049 to 1.28 × 10 -14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.

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KW - Mendelian Randomization Analysis

KW - Middle Aged

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A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

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