@article{discovery10071171,
            note = {Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.},
       publisher = {NATURE PUBLISHING GROUP},
            year = {2019},
           month = {February},
          volume = {9},
         journal = {Translational Psychiatry},
           title = {Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland},
             url = {https://doi.org/10.1038/s41398-018-0360-y},
          author = {Arnau-Soler, A and Macdonald-Dunlop, E and Adams, MJ and Clarke, T-K and MacIntyre, DJ and Milburn, K and Navrady, L and Hayward, C and McIntosh, AM and Thomson, PA and Wray, NR and Ripke, S and Mattheisen, M and Trzaskowski, M and Byrne, EM and Abdellaoui, A and Agerbo, E and Air, TM and Andlauer, TFM and Bacanu, S-A and Baekvad-Hansen, M and Beekman, ATF and Bigdeli, TB and Binder, EB and Blackwood, DHR and Bryois, J and Buttenscon, HN and Bybjerg-Grauholm, J and Cai, N and Castelao, E and Christensen, JH and Coleman, JR and Colodro-Conde, L and Couvy-Duchesne, B and Craddock, N and Rawford, GEC and Davies, G and Deary, IJ and Degenhardt, F and Derks, EM and Direk, N and Dolan, C and Dunn, EC and Eley, TC and Escott-Price, V and Kiadeh, FFH and Finucane, HK and Foo, JC and Forstner, AJ and Frank, J and Gaspar, HA and Gill, M and Goes, FS and Gordon, SD and Grove, J and Hall, LS and Hansen, CS and Hansen, TF and Herms, S and Hickie, IB and Hoffmann, P and Homuth, G and Horn, C and Hottenga, J-J and Hougaard, DM and Ising, M and Jansen, R and Jones, I and Jones, LA and Jorgenson, E and Knowles, JA and Kohane, IS and Kraft, J and Kretzschmar, WW and Krogh, J and Kutalik, Z and Li, Y and Lind, PA and Macintyre, DJ and MacKinnon, DF and Maier, RM and Maier, W and Marchini, J and Mbarek, H and McGrath, P and McGuffin, P and Medland, SE and Mehta, D and Middeldorp, CM and Mihailov, E and Milaneschi, Y and Milani, L and Mondimore, FM and Montgomery, GW and Mostafavi, S and Mullins, N and Nauck, M and Ng, B and Nivard, MG and Nyholt, DR and O'Reilly, PF and Oskarsson, H and Owen, MJ and Painter, JN and Pedersen, CB and Pedersen, MG and Peterson, RE and Pettersson, E and Peyrot, WJ and Pistis, G and Posthuma, D and Quiroz, JA and Qvist, P and Rice, JP and Riley, BP and Rivera, M and Mirza, SS and Schoevers, R and Schulte, EC and Shen, L and Shi, J and Shyn, S and Sigurdsson, E and Sinnamon, GCB and Smit, JH and Smith, DJ and Stefansson, H and Steinberg, S and Streit, F and Strohmaier, J and Tansey, KE and Teismann, H and Teumer, A and Thompson, W and Thorgeirsson, TE and Traylor, M and Treutlein, J and Trubetskoy, V and Uitterlinden, AG and Umbricht, D and Van der Auwera, S and van Hemert, AM and Viktorin, A and Visscher, PM and Wang, Y and Webb, BT and Weinsheimer, SM and Wellmann, J and Willemsen, G and Witt, SH and Wu, Y and Xi, HS and Yang, J and Zhang, F and Arolt, V and Baune, BT and Berger, K and Boomsma, D and Cichon, S and Dannlowski, U and de Geus, EJC and DePaulo, JR and Domenici, E and Domschke, K and Esko, T and Grabe, HJ and Hamilton, SP and Heath, AC and Kendler, KS and Kloiber, S and Lewis, G and Li, QS and Lucae, S and Madden, PAF and Magnusson, PK and Martin, NG and Metspalu, A and Mors, O and Mortensen, PB and Mueller-Myhsok, B and Nordentoft, M and Noethen, MM and O'Donovan, MC and Paciga, SA and Pedersen, NL and Penninx, BWJH and Perlis, RH and Porteous, DJ and Potash, JB and Preisig, M and Rietschel, M and Schaefer, C and Schulze, TG and Smoller, JW and Stefansson, K and Tiemeier, H and Uher, R and Voelzke, H and Weissman, MM and Werge, T and Lewis, CM and Levinson, DF and Breen, G and Borglum, ASD and Sullivan, PF},
        abstract = {Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p {\ensuremath{<}} 2.77 {$\times$} 10?6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 {$\times$} 10?9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 {$\times$} 10?8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p {\ensuremath{<}} 2.00 {$\times$} 10?8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p {\ensuremath{<}} 2.77 {$\times$} 10?6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 {$\times$} 10?3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.},
            issn = {2158-3188}
}