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A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank.
Shen, X. ; Howard, D. M. ; Adams, M. J. ; Hill, W. D. ; Clarke, T.-K. ; Deary, I. J. ; Whalley, H. C. ; McIntosh, A. M. (Corresponding author) ; 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. ; Bækvad-Hansen, M. ; Beekman, A. T. F. ; Bigdeli, T. B. ; Binder, E. B. ; Bryois, J. ; Buttenschøn, H. N. ; Bybjerg-Grauholm, J. ; Cai, N. ; Castelao, E. ; Christensen, J. H. ; Coleman, J. R. I. ; Colodro-Conde, L. ; Couvy-Duchesne, B. ; Craddock, N. ; Crawford, G. E. ; Davies, G. ; Degenhardt, F. ; Derks, E. M. ; Direk, N. ; Dolan, C. V. ; Dunn, E. C. ; Eley, T. C. ; Escott-Price, V. ; Kiadeh, F. F. H. ; Finucane, H. K. ; Foo, J. C. ; Forstner, A. J. ; Frank, J. ; Gaspar, H. A. ; Gill, M. ; Goes, F. S. ; Gordon, S. D. ; Grove, J. ; Hall, L. S. ; Hansen, C. S. ; Hansen, T. F. ; Herms, S. ; Hickie, I. B. ; Hoffmann, P. ; Homuth, G. ; Horn, C. ; Hottenga, J.-J. ; Hougaard, D. M. ; Howard, D. M. ; Ising, M. ; Jansen, R. ; Jones, I. ; Jones, L. A. ; Jorgenson, E. ; Knowles, J. A. ; Kohane, I. S. ; Kraft, J. ; Kretzschmar, W. W. ; Kutalik, Z. ; Li, Y. ; Lind, P. A. ; MacIntyre, D. J. ; MacKinnon, D. F. ; Maier, R. M. ; Maier, W. ; Marchini, J. ; Mbarek, H. ; McGrath, P. ; McGuffin, P. ; Medland, S. E. ; Mehta, D. ; Middeldorp, C. M. ; Mihailov, E. ; Milaneschi, Y. ; Milani, L. ; Mondimore, F. M. ; Montgomery, G. W. ; Mostafavi, S. ; Mullins, N. ; Nauck, M. ; Ng, B. ; Nivard, M. G. ; Nyholt, D. R. ; O'Reilly, P. F. ; Oskarsson, H. ; Owen, M. J. ; Painter, J. N. ; Pedersen, C. B. ; Pedersen, M. G. ; Peterson, R. E. ; Pettersson, E. ; Peyrot, W. J. ; Pistis, G. ; Posthuma, D. ; Quiroz, J. A. ; Qvist, P. ; Rice, J. P. ; Riley, B. P. ; Rivera, M. ; Mirza, S. S. ; Schoevers, R. ; Schulte, E. C. ; Shen, L. ; Shi, J. ; Shyn, S. I. ; Sigurdsson, E. ; Sinnamon, G. C. B. ; Smit, J. H. ; Smith, D. J. ; Stefansson, H. ; Steinberg, S. ; Streit, F. ; Strohmaier, J. ; Tansey, K. E. ; Teismann, H. ; Teumer, A. ; Thompson, W. ; Thomson, P. A. ; Thorgeirsson, T. E. ; Traylor, M. ; Treutlein, J. ; Trubetskoy, V. ; Uitterlinden, A. G. ; Umbricht, D. ; Auwera, S. V. d. ; van Hemert, A. M. ; Viktorin, A. ; Visscher, P. M. ; Wang, Y. ; Webb, B. T. ; Weinsheimer, S. M. ; Wellmann, J. ; Willemsen, G. ; Witt, S. H. ; Wu, Y. ; Xi, H. S. ; Yang, J. ; Zhang, F. ; Arolt, V. ; Baune, B. T. ; Berger, K. ; Boomsma, D. I. ; Cichon, S.FZJ* ; Dannlowski, U. ; de Geus, E. J. C. ; DePaulo, J. R. ; Domenici, E. ; Domschke, K. ; Esko, T. ; Grabe, H. J. ; Hamilton, S. P. ; Hayward, C. ; Heath, A. C. ; Kendler, K. S. ; Kloiber, S. ; Lewis, G. ; Li, Q. S. ; Lucae, S. ; Madden, P. A. F. ; Magnusson, P. K. ; Martin, N. G. ; Metspalu, A. ; Mors, O. ; Mortensen, P. B. ; Müller-Myhsok, B. ; Nordentoft, M. ; Nöthen, M. M. ; O'Donovan, M. C. ; Paciga, S. A. ; Pedersen, N. L. ; Penninx, B. W. J. H. ; Perlis, R. H. ; Porteous, D. J. ; Potash, J. B. ; Preisig, M. ; Rietschel, M. ; Schaefer, C. ; Schulze, T. G. ; Smoller, J. W. ; Stefansson, K. ; Tiemeier, H. ; Uher, R. ; Völzke, H. ; Weissman, M. M. ; Werge, T. ; Lewis, C. M. ; Levinson, D. F. ; Breen, G. ; Børglum, A. D. ; Sullivan, P. F.
2020
Nature Publishing Group UK
[London]
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Please use a persistent id in citations: http://hdl.handle.net/2128/24879 doi:10.1038/s41467-020-16022-0
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.
Contributing Institute(s):
- Strukturelle und funktionelle Organisation des Gehirns (INM-1)
Research Program(s):
- 571 - Connectivity and Activity (POF3-571) (POF3-571)
Appears in the scientific report
2020
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