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

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Harvard

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

APA

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

CBE

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. 11(1):2301. https://doi.org/10.1038/s41467-020-16022-0

MLA

Vancouver

Author

Shen, Xueyi ; Howard, David M. ; Adams, Mark J. ; Hill, W. David ; Clarke, Toni Kim ; Adams, Mark J. ; Clarke, Toni Kim ; McIntosh, Andrew M. ; Deary, Ian J. ; Wray, Naomi R. ; Ripke, Stephan ; Mattheisen, Manuel ; Trzaskowski, Maciej ; Byrne, Enda M. ; Abdellaoui, Abdel ; Agerbo, Esben ; Air, Tracy M. ; Andlauer, Till F.M. ; Bacanu, Silviu Alin ; Bækvad-Hansen, Marie ; Beekman, Aartjan T.F. ; Bigdeli, Tim B. ; Binder, Elisabeth B. ; Bryois, Julien ; Buttenschøn, Henriette N. ; Bybjerg-Grauholm, Jonas ; Cai, Na ; Castelao, Enrique ; Christensen, Jane Hvarregaard ; Coleman, Jonathan R.I. ; Colodro-Conde, Lucía ; Couvy-Duchesne, Baptiste ; Craddock, Nick ; Crawford, Gregory E. ; Davies, Gail ; Degenhardt, Franziska ; Derks, Eske M. ; Direk, Nese ; Dolan, Conor V. ; Dunn, Erin C. ; Eley, Thalia C. ; Escott-Price, Valentina ; Kiadeh, Farnush Farhadi Hassan ; Finucane, Hilary K. ; Foo, Jerome C. ; Hansen, Thomas F. ; Thompson, Wesley ; Weinsheimer, Shantel Marie ; Nordentoft, Merete ; Werge, Thomas ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. / A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank. I: Nature Communications. 2020 ; Bind 11, Nr. 1. s. 2301.

Bibtex

@article{883663a015c546a492e5f1f6bf3a13b5,
title = "A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank",
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. ",
keywords = "Aged, Biological Specimen Banks, Depression/genetics, Female, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Neuroimaging/methods, Polymorphism, Single Nucleotide/genetics, Prefrontal Cortex/metabolism, Risk Factors",
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}",
year = "2020",
month = may,
day = "8",
doi = "10.1038/s41467-020-16022-0",
language = "English",
volume = "11",
pages = "2301",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

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.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Bryois, Julien

AU - Buttenschøn, Henriette N.

AU - Bybjerg-Grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

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.

AU - Thompson, Wesley

AU - Weinsheimer, Shantel Marie

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

PY - 2020/5/8

Y1 - 2020/5/8

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.

AB - 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.

KW - Aged

KW - Biological Specimen Banks

KW - Depression/genetics

KW - Female

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Mendelian Randomization Analysis

KW - Middle Aged

KW - Neuroimaging/methods

KW - Polymorphism, Single Nucleotide/genetics

KW - Prefrontal Cortex/metabolism

KW - Risk Factors

UR - http://www.scopus.com/inward/record.url?scp=85084721245&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-16022-0

DO - 10.1038/s41467-020-16022-0

M3 - Journal article

C2 - 32385265

AN - SCOPUS:85084721245

VL - 11

SP - 2301

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -

ID: 60936025