Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium

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From: Biological Psychiatry(Vol. 84, Issue 2)
Publisher: Elsevier B.V.
Document Type: Report
Length: 1,614 words

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Keywords Childhood trauma; Depression; Genetics; Interaction; Meta-analysis; Polygenic risk Abstract Background The heterogeneity of genetic effects on major depressive disorder (MDD) may be partly attributable to moderation of genetic effects by environment, such as exposure to childhood trauma (CT). Indeed, previous findings in two independent cohorts showed evidence for interaction between polygenic risk scores (PRSs) and CT, albeit in opposing directions. This study aims to meta-analyze MDD-PRS x CT interaction results across these two and other cohorts, while applying more accurate PRSs based on a larger discovery sample. Methods Data were combined from 3024 MDD cases and 2741 control subjects from nine cohorts contributing to the MDD Working Group of the Psychiatric Genomics Consortium. MDD-PRS were based on a discovery sample of ~110,000 independent individuals. CT was assessed as exposure to sexual or physical abuse during childhood. In a subset of 1957 cases and 2002 control subjects, a more detailed five-domain measure additionally included emotional abuse, physical neglect, and emotional neglect. Results MDD was associated with the MDD-PRS (odds ratio [OR] = 1.24, p = 3.6 x 10.sup.-5, R.sup.2 = 1.18%) and with CT (OR = 2.63, p = 3.5 x 10.sup.-18 and OR = 2.62, p = 1.4 x10.sup.-5 for the two- and five-domain measures, respectively). No interaction was found between MDD-PRS and the two-domain and five-domain CT measure (OR = 1.00, p = .89 and OR = 1.05, p = .66). Conclusions No meta-analytic evidence for interaction between MDD-PRS and CT was found. This suggests that the previously reported interaction effects, although both statistically significant, can best be interpreted as chance findings. Further research is required, but this study suggests that the genetic heterogeneity of MDD is not attributable to genome-wide moderation of genetic effects by CT. Author Affiliation: (a) Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands (b) Department of Biological Psychology, VU University Medical Center, Amsterdam, the Netherlands (c) Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany (d) Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany (e) Department of Psychiatry and Psychotherapy, Charite--Universitatsmedizin, Berlin, Germany (f) Department of Psychiatry, Washington University Medical School, St. Louis, Missouri (g) Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (h) Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts (i) Department of Psychiatry, Harvard Medical School, Boston, Massachusetts (j) Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California (k) Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK (l) Queensland Brain Institute, University of Queensland, Brisbane, Australia (m) Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia (n) Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Australia (o) Discipline of Psychiatry, University of Adelaide, Adelaide, Australia * Address correspondence to Wouter J. Peyrot, M.D., VU University Medical Center and GGZ inGeest, Department of Psychiatry, AJ Ernststraat 1187, Amsterdam 1081 HL, Netherlands. Article History: Received 21 May 2017; Revised 1 September 2017; Accepted 1 September 2017 (footnote) The Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium is a collaborative co-author for this article. The individual authors are (affiliations are listed in the ) 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 Baekvad-Hansen, Aartjan T. F. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Douglas H. R. Blackwood, Julien Bryois, Henriette N. Buttenschon, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan R. I. Coleman, Lucia 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, Andreas J. Forstner, Josef Frank, Helena A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Soholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hicki, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Hougaard, Marcus Ising, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Jesper Krogh, Zoltan 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 Bocker Pedersen, Marianne Giortz 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, Andre 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, Jurgen 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, Tonu 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 Muller-Myhsok, Merete Nordentoft, Markus M. Nothen, 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 Volzke, Myrna M. Weissman, Thomas Werge, Cathryn M. Lewis, Douglas F. Levinson, Gerome Breen, Anders D. Borglum, and Patrick F. Sullivan. (footnote)1 HJG, NRW, and BWJHP contributed equally to this work. Byline: Wouter J. Peyrot [peyrot.w@gmail.com] (a,*), Sandra Van der Auwera (c), Yuri Milaneschi (a), Conor V. Dolan (b), Pamela A.F. Madden (f), Patrick F. Sullivan (g), Jana Strohmaier (d), Stephan Ripke (e,h), Marcella Rietschel (d), Michel G. Nivard (b), Niamh Mullins (k), Grant W. Montgomery (l,m), Anjali K. Henders (l,m), Andrew C. Heat (f), Helen L. Fisher (k), Erin C. Dunn (i), Enda M. Byrne (l,m), Tracy A. Air (o), 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 Baekvad-Hansen, Aartjan T.F. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Douglas H.R. Blackwood, Julien Bryois, Henriette N. Buttenschon, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan R.I. Coleman, Lucia 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, Andreas J. Forstner, Josef Frank, Helena A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Soholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hicki, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Hougaard, Marcus Ising, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Jesper Krogh, Zoltan 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 Bocker Pedersen, Marianne Giortz 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, Andre 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, Jurgen 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, Tonu 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 Muller-Myhsok, Merete Nordentoft, Markus M. Nothen, 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 Volzke, Myrna M. Weissman, Thomas Werge, Cathryn M. Lewis, Douglas F. Levinson, Gerome Breen, Anders D. Borglum, Patrick F. Sullivan

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Gale Document Number: GALE|A544805286