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, pFDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, pFDR: 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.
Original language | English |
---|---|
Article number | 2301 |
Journal | Nature Communications |
Volume | 11 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Dec 2020 |
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A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank. / Shen, Xueyi; Howard, David M.; Adams, Mark J. et al.
In: Nature Communications, Vol. 11, No. 1, 2301, 01.12.2020.Research output: Contribution to journal › Article › Academic › peer-review
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 - 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 - Forstner, Andreas J.
AU - Frank, Josef
AU - Gaspar, Héléna A.
AU - Gill, Michael
AU - Goes, Fernando S.
AU - Gordon, Scott D.
AU - Grove, Jakob
AU - Hall, Lynsey S.
AU - Hansen, Christine Søholm
AU - Hansen, Thomas F.
AU - Herms, Stefan
AU - Hickie, Ian B.
AU - Hoffmann, Per
AU - Homuth, Georg
AU - Horn, Carsten
AU - Hottenga, Jouke Jan
AU - Hougaard, David M.
AU - Ising, Marcus
AU - Jansen, Rick
AU - Jones, Ian
AU - Jones, Lisa A.
AU - Jorgenson, Eric
AU - Knowles, James A.
AU - Kohane, Isaac S.
AU - Kraft, Julia
AU - Kretzschmar, Warren W.
AU - Kutalik, Zoltán
AU - Li, Yihan
AU - Lind, Penelope A.
AU - MacIntyre, Donald J.
AU - MacKinnon, Dean F.
AU - Maier, Robert M.
AU - Maier, Wolfgang
AU - Marchini, Jonathan
AU - Mbarek, Hamdi
AU - McGrath, Patrick
AU - McGuffin, Peter
AU - Medland, Sarah E.
AU - Mehta, Divya
AU - Middeldorp, Christel M.
AU - Mihailov, Evelin
AU - Milaneschi, Yuri
AU - Milani, Lili
AU - Mondimore, Francis M.
AU - Montgomery, Grant W.
AU - Mostafavi, Sara
AU - Mullins, Niamh
AU - Nauck, Matthias
AU - Ng, Bernard
AU - Nivard, Michel G.
AU - Nyholt, Dale R.
AU - O’Reilly, Paul F.
AU - Oskarsson, Hogni
AU - Owen, Michael J.
AU - Painter, Jodie N.
AU - Pedersen, Carsten Bøcker
AU - Pedersen, Marianne Giørtz
AU - Peterson, Roseann E.
AU - Pettersson, Erik
AU - Peyrot, Wouter J.
AU - Pistis, Giorgio
AU - Posthuma, Danielle
AU - Quiroz, Jorge A.
AU - Qvist, Per
AU - Rice, John P.
AU - Riley, Brien P.
AU - Rivera, Margarita
AU - Mirza, Saira Saeed
AU - Schoevers, Robert
AU - Schulte, Eva C.
AU - Shen, Ling
AU - Shi, Jianxin
AU - Shyn, Stanley I.
AU - Sigurdsson, Engilbert
AU - Sinnamon, Grant C.B.
AU - Smit, Johannes H.
AU - Smith, Daniel J.
AU - Stefansson, Hreinn
AU - Steinberg, Stacy
AU - Streit, Fabian
AU - Strohmaier, Jana
AU - Tansey, Katherine E.
AU - Teismann, Henning
AU - Teumer, Alexander
AU - Thompson, Wesley
AU - Thomson, Pippa A.
AU - Thorgeirsson, Thorgeir E.
AU - Traylor, Matthew
AU - Treutlein, Jens
AU - Trubetskoy, Vassily
AU - Uitterlinden, Andrés G.
AU - Umbricht, Daniel
AU - Auwera, Sandra Van der
AU - van Hemert, Albert M.
AU - Viktorin, Alexander
AU - Visscher, Peter M.
AU - Wang, Yunpeng
AU - Webb, Bradley T.
AU - Weinsheimer, Shantel Marie
AU - Wellmann, Jürgen
AU - Willemsen, Gonneke
AU - Witt, Stephanie H.
AU - Wu, Yang
AU - Xi, Hualin S.
AU - Yang, Jian
AU - Zhang, Futao
AU - Arolt, Volker
AU - Baune, Bernhard T.
AU - Berger, Klaus
AU - Boomsma, Dorret I.
AU - Cichon, Sven
AU - Dannlowski, Udo
AU - de Geus, E. J.C.
AU - DePaulo, J. Raymond
AU - Domenici, Enrico
AU - Domschke, Katharina
AU - Esko, Tõnu
AU - Grabe, Hans J.
AU - Hamilton, Steven P.
AU - Hayward, Caroline
AU - Heath, Andrew C.
AU - Kendler, Kenneth S.
AU - Kloiber, Stefan
AU - Lewis, Glyn
AU - Li, Qingqin S.
AU - Lucae, Susanne
AU - Madden, Pamela A.F.
AU - Magnusson, Patrik K.
AU - Martin, Nicholas G.
AU - Metspalu, Andres
AU - Mors, Ole
AU - Mortensen, Preben Bo
AU - Müller-Myhsok, Bertram
AU - Nordentoft, Merete
AU - Nöthen, Markus M.
AU - O’Donovan, Michael C.
AU - Paciga, Sara A.
AU - Pedersen, Nancy L.
AU - Penninx, Brenda W.J.H.
AU - Perlis, Roy H.
AU - Porteous, David J.
AU - Potash, James B.
AU - Preisig, Martin
AU - Rietschel, Marcella
AU - Schaefer, Catherine
AU - Schulze, Thomas G.
AU - Smoller, Jordan W.
AU - Stefansson, Kari
AU - Tiemeier, Henning
AU - Uher, Rudolf
AU - Völzke, Henry
AU - Weissman, Myrna M.
AU - Werge, Thomas
AU - Lewis, Cathryn M.
AU - Levinson, Douglas F.
AU - Breen, Gerome
AU - Børglum, Anders D.
AU - Sullivan, Patrick F.
AU - Whalley, Heather C.
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
PY - 2020/12/1
Y1 - 2020/12/1
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, pFDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, pFDR: 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, pFDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, pFDR: 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.
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 - Article
C2 - 32385265
AN - SCOPUS:85084721245
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2301
ER -