Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

Jonathan R.I. Coleman; Wouter J. Peyrot; Kirstin L. Purves; Katrina A.S. Davis; Christopher Rayner; Shing Wan Choi; Christopher Hübel; Héléna A. Gaspar; Carol Kan; Sandra Van der Auwera; Mark James Adams; Donald M. Lyall; Karmel W. Choi; Naomi R. Wray; Stephan Ripke; Manuel Mattheisen; Maciej Trzaskowski; Enda M. Byrne; Abdel Abdellaoui; Mark J. Adams; Esben Agerbo; Tracy M. Air; Till F.M. Andlauer; Silviu Alin Bacanu; Marie Bækvad-Hansen; Aartjan T.F. Beekman; Tim B. Bigdeli; Elisabeth B. Binder; Julien Bryois; Henriette N. Buttenschøn; Jonas Bybjerg-Grauholm; Na Cai; Enrique Castelao; Jane Hvarregaard Christensen; Toni Kim Clarke; Jonathan R.I. Coleman; Lucía Colodro-Conde; Baptiste Couvy-Duchesne; Nick Craddock; Gregory E. Crawford; Gail Davies; Ian J. Deary; Franziska Degenhardt; Eske M. Derks; Nese Direk; Conor V. Dolan; Erin C. Dunn; Thalia C. Eley; Valentina Escott-Price; Farnush Farhadi Hassan Kiadeh; Hilary K. Finucane; Jerome C. Foo; Andreas J. Forstner; Josef Frank; Héléna A. Gaspar; Michael Gill; Fernando S. Goes; Scott D. Gordon; Jakob Grove; Lynsey S. Hall; Christine Søholm Hansen; Thomas F. Hansen; Stefan Herms; Ian B. Hickie; Per Hoffmann; Georg Homuth; Carsten Horn; Jouke Jan Hottenga; David M. Hougaard; David M. Howard; Marcus Ising; Rick Jansen; Ian Jones; Lisa A. Jones; Eric Jorgenson; James A. Knowles; Isaac S. Kohane; Julia Kraft; Warren W. Kretzschmar; Zoltán Kutalik; Yihan Li; Penelope A. Lind; Donald J. MacIntyre; Dean F. MacKinnon; Robert M. Maier; Wolfgang Maier; Jonathan Marchini; Hamdi Mbarek; Patrick McGrath; Peter McGuffin; Sarah E. Medland; Divya Mehta; Christel M. Middeldorp; Evelin Mihailov; Yuri Milaneschi; Lili Milani; Francis M. Mondimore; Grant W. Montgomery; Sara Mostafavi; Niamh Mullins; Matthias Nauck; Bernard Ng; Michel G. Nivard; Dale R. Nyholt; Paul F. O’Reilly; Hogni Oskarsson; Michael J. Owen; Jodie N. Painter; Carsten Bøcker Pedersen; Marianne Giørtz Pedersen; Roseann E. Peterson; Erik Pettersson; Wouter J. Peyrot; Giorgio Pistis; Danielle Posthuma; Jorge A. Quiroz; Per Qvist; John P. Rice; Brien P. Riley; Margarita Rivera; Saira Saeed Mirza; Robert Schoevers; Eva C. Schulte; Ling Shen; Jianxin Shi; Stanley I. Shyn; Engilbert Sigurdsson; Grant C.B. Sinnamon; Johannes H. Smit; Daniel J. Smith; Hreinn Stefansson; Stacy Steinberg; Fabian Streit; Jana Strohmaier; Katherine E. Tansey; Henning Teismann; Alexander Teumer; Wesley Thompson; Pippa A. Thomson; Thorgeir E. Thorgeirsson; Matthew Traylor; Jens Treutlein; Vassily Trubetskoy; Andrés G. Uitterlinden; Daniel Umbricht; Sandra Van der Auwera; Albert M. van Hemert; Alexander Viktorin; Peter M. Visscher; Yunpeng Wang; Bradley T. Webb; Shantel Marie Weinsheimer; Jürgen Wellmann; Gonneke Willemsen; Stephanie H. Witt; Yang Wu; Hualin S. Xi; Jian Yang; Futao Zhang; Volker Arolt; Bernhard T. Baune; Klaus Berger; Dorret I. Boomsma; Sven Cichon; Udo Dannlowski; E. J.C. de Geus; J. Raymond DePaulo; Enrico Domenici; Katharina Domschke; Tõnu Esko; Hans J. Grabe; Steven P. Hamilton; Caroline Hayward; Andrew C. Heath; Kenneth S. Kendler; Stefan Kloiber; Glyn Lewis; Qingqin S. Li; Susanne Lucae; Pamela A.F. Madden; Patrik K. Magnusson; Nicholas G. Martin; Andrew M. McIntosh; Andres Metspalu; Ole Mors; Preben Bo Mortensen; Bertram Müller-Myhsok; Merete Nordentoft; Markus M. Nöthen; Michael C. O’Donovan; Sara A. Paciga; Nancy L. Pedersen; Brenda W.J.H. Penninx; Roy H. Perlis; David J. Porteous; James B. Potash; Martin Preisig; Marcella Rietschel; Catherine Schaefer; Thomas G. Schulze; Jordan W. Smoller; Kari Stefansson; Henning Tiemeier; Rudolf Uher; Henry Völzke; Myrna M. Weissman; Thomas Werge; Cathryn M. Lewis; Douglas F. Levinson; Gerome Breen; Anders D. Børglum; Patrick F. Sullivan; Erin C. Dunn; Evangelos Vassos; Andrea Danese; Barbara Maughan; Hans J. Grabe; Cathryn M. Lewis; Paul F. O’Reilly; Andrew M. McIntosh; Daniel J. Smith; Naomi R. Wray; Matthew Hotopf; Thalia C. Eley; Gerome Breen; on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1038/s41380-019-0546-6

Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

Jonathan R.I. Coleman, Wouter J. Peyrot, Kirstin L. Purves, Katrina A.S. Davis, Christopher Rayner, Shing Wan Choi, Christopher Hübel, Héléna A. Gaspar, Carol Kan, Sandra Van der Auwera, Mark James Adams, Donald M. Lyall, Karmel W. Choi, Naomi R. Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. AdamsEsben Agerbo, Tracy M. Air, Till F.M. Andlauer, Silviu Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni Kim Clarke, Jonathan R.I. Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Ian J. Deary, Franziska Degenhardt, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley^*, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Andreas J. Forstner, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke Jan Hottenga, David M. Hougaard, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E. Medland, Divya Mehta, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Michael J. Owen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Erik Pettersson, Wouter J. Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Jianxin Shi, Stanley I. Shyn, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, Andrés G. Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H. Witt, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T. Baune, Klaus Berger, Dorret I. Boomsma, Sven Cichon, Udo Dannlowski, E. J.C. de Geus, J. Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J. Grabe, Steven P. Hamilton, Caroline Hayward, Andrew C. Heath, Kenneth S. Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S. Li, Susanne Lucae, Pamela A.F. Madden, Patrik K. Magnusson, Nicholas G. Martin, Andrew M. McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M. Nöthen, Michael C. O’Donovan, Sara A. Paciga, Nancy L. Pedersen, Brenda W.J.H. Penninx, Roy H. Perlis, David J. Porteous, James B. Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G. Schulze, Jordan W. Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M. Weissman, Thomas Werge, Cathryn M. Lewis, Douglas F. Levinson, Gerome Breen, Anders D. Børglum, Patrick F. Sullivan, Erin C. Dunn, Evangelos Vassos, Andrea Danese, Barbara Maughan, Hans J. Grabe, Cathryn M. Lewis, Paul F. O’Reilly, Andrew M. McIntosh, Daniel J. Smith, Naomi R. Wray, Matthew Hotopf, Thalia C. Eley, Gerome Breen, on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094–92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10−7 versus rg = −0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10−4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

Original language	English
Pages (from-to)	1430-1446
Number of pages	17
Journal	Molecular Psychiatry
Volume	25
Issue number	7
Early online date	23 Jan 2020
DOIs	https://doi.org/10.1038/s41380-019-0546-6
Publication status	Published - 1 Jul 2020

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10.1038/s41380-019-0546-6

Cite this

Coleman, J. R. I., Peyrot, W. J., Purves, K. L., Davis, K. A. S., Rayner, C., Choi, S. W., Hübel, C., Gaspar, H. A., Kan, C., Van der Auwera, S., Adams, M. J., Lyall, D. M., Choi, K. W., Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., ... on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2020). Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank. Molecular Psychiatry, 25(7), 1430-1446. https://doi.org/10.1038/s41380-019-0546-6

@article{082de5a256e441d29d6086fdd295f4b6,

title = "Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank",

abstract = "Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094–92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10−7 versus rg = −0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10−4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.",

author = "Coleman, {Jonathan R.I.} and Peyrot, {Wouter J.} and Purves, {Kirstin L.} and Davis, {Katrina A.S.} and Christopher Rayner and Choi, {Shing Wan} and Christopher H{\"u}bel and Gaspar, {H{\'e}l{\'e}na A.} and Carol Kan and {Van der Auwera}, Sandra and Adams, {Mark James} and Lyall, {Donald M.} and Choi, {Karmel W.} and Wray, {Naomi R.} and Stephan Ripke and Manuel Mattheisen and Maciej Trzaskowski and Byrne, {Enda M.} and Abdel Abdellaoui and Adams, {Mark J.} and Esben Agerbo and Air, {Tracy M.} and Andlauer, {Till F.M.} and Bacanu, {Silviu Alin} and Marie B{\ae}kvad-Hansen and Beekman, {Aartjan T.F.} and Bigdeli, {Tim B.} and Binder, {Elisabeth B.} and Julien Bryois and Buttensch{\o}n, {Henriette N.} and Jonas Bybjerg-Grauholm and Na Cai and Enrique Castelao and Christensen, {Jane Hvarregaard} and Clarke, {Toni Kim} and Coleman, {Jonathan R.I.} and Luc{\'i}a Colodro-Conde and Baptiste Couvy-Duchesne and Nick Craddock and Crawford, {Gregory E.} and Gail Davies and Deary, {Ian J.} and Franziska Degenhardt and Derks, {Eske M.} and Nese Direk and Dolan, {Conor V.} and Dunn, {Erin C.} and Eley, {Thalia C.} and Valentina Escott-Price and Kiadeh, {Farnush Farhadi Hassan} and Finucane, {Hilary K.} and Foo, {Jerome C.} and Forstner, {Andreas J.} and Josef Frank and Gaspar, {H{\'e}l{\'e}na A.} and Michael Gill and Goes, {Fernando S.} and Gordon, {Scott D.} and Jakob Grove and Hall, {Lynsey S.} and Hansen, {Christine S{\o}holm} and Hansen, {Thomas F.} and Stefan Herms and Hickie, {Ian B.} and Per Hoffmann and Georg Homuth and Carsten Horn and Hottenga, {Jouke Jan} and Hougaard, {David M.} and Howard, {David M.} and Marcus Ising and Rick Jansen and Ian Jones and Jones, {Lisa A.} and Eric Jorgenson and Knowles, {James A.} and Kohane, {Isaac S.} and Julia Kraft and Kretzschmar, {Warren W.} and Zolt{\'a}n Kutalik and Yihan Li and Lind, {Penelope A.} and MacIntyre, {Donald J.} and MacKinnon, {Dean F.} and Maier, {Robert M.} and Wolfgang Maier and Jonathan Marchini and Hamdi Mbarek and Patrick McGrath and Peter McGuffin and Medland, {Sarah E.} and Divya Mehta and Middeldorp, {Christel M.} and Evelin Mihailov and Yuri Milaneschi and Lili Milani and Mondimore, {Francis M.} and Montgomery, {Grant W.} and Sara Mostafavi and Niamh Mullins and Matthias Nauck and Bernard Ng and Nivard, {Michel G.} and Nyholt, {Dale R.} and O{\textquoteright}Reilly, {Paul F.} and Hogni Oskarsson and Owen, {Michael J.} and Painter, {Jodie N.} and Pedersen, {Carsten B{\o}cker} and Pedersen, {Marianne Gi{\o}rtz} and Peterson, {Roseann E.} and Erik Pettersson and Peyrot, {Wouter J.} and Giorgio Pistis and Danielle Posthuma and Quiroz, {Jorge A.} and Per Qvist and Rice, {John P.} and Riley, {Brien P.} and Margarita Rivera and Mirza, {Saira Saeed} and Robert Schoevers and Schulte, {Eva C.} and Ling Shen and Jianxin Shi and Shyn, {Stanley I.} and Engilbert Sigurdsson and Sinnamon, {Grant C.B.} and Smit, {Johannes H.} and Smith, {Daniel J.} and Hreinn Stefansson and Stacy Steinberg and Fabian Streit and Jana Strohmaier and Tansey, {Katherine E.} and Henning Teismann and Alexander Teumer and Wesley Thompson and Thomson, {Pippa A.} and Thorgeirsson, {Thorgeir E.} and Matthew Traylor and Jens Treutlein and Vassily Trubetskoy and Uitterlinden, {Andr{\'e}s G.} and Daniel Umbricht and {Van der Auwera}, Sandra and {van Hemert}, {Albert M.} and Alexander Viktorin and Visscher, {Peter M.} and Yunpeng Wang and Webb, {Bradley T.} and Weinsheimer, {Shantel Marie} and J{\"u}rgen Wellmann and Gonneke Willemsen and Witt, {Stephanie H.} and Yang Wu and Xi, {Hualin S.} and Jian Yang and Futao Zhang and Volker Arolt and Baune, {Bernhard T.} and Klaus Berger and Boomsma, {Dorret I.} and Sven Cichon and Udo Dannlowski and {de Geus}, {E. J.C.} and DePaulo, {J. Raymond} and Enrico Domenici and Katharina Domschke and T{\~o}nu Esko and Grabe, {Hans J.} and Hamilton, {Steven P.} and Caroline Hayward and Heath, {Andrew C.} and Kendler, {Kenneth S.} and Stefan Kloiber and Glyn Lewis and Li, {Qingqin S.} and Susanne Lucae and Madden, {Pamela A.F.} and Magnusson, {Patrik K.} and Martin, {Nicholas G.} and McIntosh, {Andrew M.} and Andres Metspalu and Ole Mors and Mortensen, {Preben Bo} and Bertram M{\"u}ller-Myhsok and Merete Nordentoft and N{\"o}then, {Markus M.} and O{\textquoteright}Donovan, {Michael C.} and Paciga, {Sara A.} and Pedersen, {Nancy L.} and Penninx, {Brenda W.J.H.} and Perlis, {Roy H.} and Porteous, {David J.} and Potash, {James B.} and Martin Preisig and Marcella Rietschel and Catherine Schaefer and Schulze, {Thomas G.} and Smoller, {Jordan W.} and Kari Stefansson and Henning Tiemeier and Rudolf Uher and Henry V{\"o}lzke and Weissman, {Myrna M.} and Thomas Werge and Lewis, {Cathryn M.} and Levinson, {Douglas F.} and Gerome Breen and B{\o}rglum, {Anders D.} and Sullivan, {Patrick F.} and Dunn, {Erin C.} and Evangelos Vassos and Andrea Danese and Barbara Maughan and Grabe, {Hans J.} and Lewis, {Cathryn M.} and O{\textquoteright}Reilly, {Paul F.} and McIntosh, {Andrew M.} and Smith, {Daniel J.} and Wray, {Naomi R.} and Matthew Hotopf and Eley, {Thalia C.} and Gerome Breen and {on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",

year = "2020",

month = jul,

day = "1",

doi = "10.1038/s41380-019-0546-6",

language = "English",

volume = "25",

pages = "1430--1446",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

number = "7",

}

Coleman, JRI, Peyrot, WJ, Purves, KL, Davis, KAS, Rayner, C, Choi, SW, Hübel, C, Gaspar, HA, Kan, C, Van der Auwera, S, Adams, MJ, Lyall, DM, Choi, KW, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, 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, Clarke, TK, Coleman, JRI, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, 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, Howard, 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, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Müller-Myhsok, B, Nordentoft, M, Nöthen, MM, O’Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Völzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Børglum, AD, Sullivan, PF, Dunn, EC, Vassos, E, Danese, A, Maughan, B, Grabe, HJ, Lewis, CM, O’Reilly, PF, McIntosh, AM, Smith, DJ, Wray, NR, Hotopf, M, Eley, TC, Breen, G & on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2020, 'Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank', Molecular Psychiatry, vol. 25, no. 7, pp. 1430-1446. https://doi.org/10.1038/s41380-019-0546-6

TY - JOUR

T1 - Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

AU - Coleman, Jonathan R.I.

AU - Peyrot, Wouter J.

AU - Purves, Kirstin L.

AU - Davis, Katrina A.S.

AU - Rayner, Christopher

AU - Choi, Shing Wan

AU - Hübel, Christopher

AU - Gaspar, Héléna A.

AU - Kan, Carol

AU - Van der Auwera, Sandra

AU - Adams, Mark James

AU - Lyall, Donald M.

AU - Choi, Karmel W.

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

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 - Clarke, Toni Kim

AU - Coleman, Jonathan R.I.

AU - Colodro-Conde, Lucía

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Davies, Gail

AU - Deary, Ian J.

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 - Howard, 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

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AU - on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

PY - 2020/7/1

Y1 - 2020/7/1

N2 - Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094–92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10−7 versus rg = −0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10−4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

AB - Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094–92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10−7 versus rg = −0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10−4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85078355026&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31969693

UR - http://www.scopus.com/inward/record.url?scp=85078355026&partnerID=8YFLogxK

U2 - 10.1038/s41380-019-0546-6

DO - 10.1038/s41380-019-0546-6

M3 - Article

C2 - 31969693

VL - 25

SP - 1430

EP - 1446

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 7

ER -

Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

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