| Title: |
A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank |
| Authors: |
Shen, X; Howard, DM; Adams, MJ; Hill, WD; 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; Forstner, AJ; Frank, J; Gaspar, HA; Gill, M; Goes, FS; Gordon, SD; Grove, J; Hall, LS; Hansen, CS; Hansen, TF; Herms, S; Hickie, IB; Hoffmann, P; Homuth, G; Horn, C; Hottenga, JJ; Hougaard, DM; Ising, M; Jansen, R; Jones, I; Jones, LA; Jorgenson, E; Knowles, JA; Kohane, IS; Kraft, J; Kretzschmar, WW; Kutalik, Z; Li, Y; Lind, PA; MacIntyre, DJ; MacKinnon, DF; Maier, RM; Maier, W; Marchini, J; Mbarek, H; McGrath, P; McGuffin, P; Medland, SE; Mehta, D; Middeldorp, CM; Mihailov, E; Milaneschi, Y; Milani, L; Mondimore, FM; Montgomery, GW; Mostafavi, S; Mullins, N; Nauck, M; Ng, B; Nivard, MG; Nyholt, DR; O’Reilly, PF; Oskarsson, H; Owen, MJ; Painter, JN; Pedersen, CB; Pedersen, MG |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2020 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://hdl.handle.net/11343/246479 |
| Availability: |
https://hdl.handle.net/11343/246479 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.8F1F78EA |
| Database: |
BASE |