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 - Deary, Ian J
AU - Whalley, Heather C
AU - McIntosh, Andrew M
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
AU - Abdellaoui, A.
AU - Derks, Eske M.
AU - Dolan, C.V.
AU - Hottenga, Jouke Jan
AU - Jansen, Rick
AU - Mbarek, Hamdi
AU - Middeldorp, C.M.
AU - Nivard, Michel
AU - Peyrot, Wouter J
AU - Posthuma, Danielle
AU - Willemsen, Gonneke
AU - Boomsma, D.I.
AU - de Geus, Eco J.C.
AU - W J H Penninx, Brenda
AU - Wray, Naomi R.
AU - Ripke, Stephan
AU - Mattheisen, Manuel
AU - Trzaskowski, Maciej
AU - Byrne, Enda M.
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 - Direk, Nese
AU - Dunn, Erin C.
AU - Eley, Thalia C.
AU - Escott-Price, Valentina
AU - Kiadeh, Farnush Farhadi Hassan
AU - Milaneschi, Yuri
AU - Schoevers, Robert
AU - Smit, Johannes H.
AU - Finucane, Hilary K.
AU - Foo, Jerome C.
AU - Forstner, Andreas J.
AU - Frank, Josef
AU - Gaspar, H. léna A.
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, 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.
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U2 - https://doi.org/10.1038/s41467-020-16022-0
DO - https://doi.org/10.1038/s41467-020-16022-0
M3 - Article
C2 - 32385265
SN - 2041-1723
VL - 11
SP - 2301
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2301
ER -