. 2020 Jul;25(7):1430-1446.

doi: 10.1038/s41380-019-0546-6. Epub 2020 Jan 23.

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

Jonathan R I Coleman^{1

2}, Wouter J Peyrot³, Kirstin L Purves¹, Katrina A S Davis^{2

4}, Christopher Rayner¹, Shing Wan Choi¹, Christopher Hübel^{1

2}, Héléna A Gaspar^{1

2}, Carol Kan⁴, Sandra Van der Auwera⁵, Mark James Adams⁶, Donald M Lyall⁷, Karmel W Choi^{8

9

10

11}; on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Erin C Dunn^{10

11

12}, Evangelos Vassos^{1

2}, Andrea Danese^{1

13

14}, Barbara Maughan¹, Hans J Grabe⁵, Cathryn M Lewis^{1

2}, Paul F O'Reilly¹, Andrew M McIntosh⁶, Daniel J Smith⁷, Naomi R Wray^{15

16}, Matthew Hotopf^{2

4}, Thalia C Eley^{17

18}, Gerome Breen^{19

20}

Collaborators, Affiliations

Collaborators

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

Affiliations

¹ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
² NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK.
³ Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
⁴ Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁵ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
⁶ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
⁷ Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
⁸ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
⁹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁰ Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
¹¹ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹² Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
¹³ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
¹⁴ National and Specialist CAMHS Trauma and Anxiety Clinic, South London and Maudsley NHS Foundation Trust, London, UK.
¹⁵ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
¹⁶ Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
¹⁷ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. thalia.eley@kcl.ac.uk.
¹⁸ NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. thalia.eley@kcl.ac.uk.
¹⁹ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. gerome.breen@kcl.ac.uk.
²⁰ NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. gerome.breen@kcl.ac.uk.

PMID: 31969693
PMCID: PMC7305950
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 et al. Mol Psychiatry. 2020 Jul.

. 2020 Jul;25(7):1430-1446.

doi: 10.1038/s41380-019-0546-6. Epub 2020 Jan 23.

Authors

Collaborators

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

Affiliations

¹ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
² NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK.
³ Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
⁴ Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁵ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
⁶ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
⁷ Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
⁸ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
⁹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁰ Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
¹¹ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹² Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
¹³ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
¹⁴ National and Specialist CAMHS Trauma and Anxiety Clinic, South London and Maudsley NHS Foundation Trust, London, UK.
¹⁵ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
¹⁶ Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
¹⁷ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. thalia.eley@kcl.ac.uk.
¹⁸ NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. thalia.eley@kcl.ac.uk.
¹⁹ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. gerome.breen@kcl.ac.uk.
²⁰ NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. gerome.breen@kcl.ac.uk.

PMID: 31969693
PMCID: PMC7305950
DOI: 10.1038/s41380-019-0546-6

Erratum in

Correction: Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank.
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; on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; 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. Coleman JRI, et al. Mol Psychiatry. 2021 Sep;26(9):5465. doi: 10.1038/s41380-020-0779-4. Mol Psychiatry. 2021. PMID: 32424234 No abstract available.

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 (r_g = 0.24, p = 1.8 × 10^-7 versus r_g = -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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

No authors report a conflict of interest associated with the research presented in this paper.

Figures

**Figure 1:**
Genetic correlations between MDD (overall and stratified by reported trauma exposure) and selected traits and disorders. Full genetic correlation results are available in Supplementary Table 9. Numbers = genetic correlations. Colour = direction of effect (blue = positive, red = negative). Colour intensity = size of correlation. Upper and lower bars are 95% confidence interval of genetic correlation.

**Figure 2:**
Association between MDD polygenic risk score (PRS) and MDD. Individuals reporting trauma exposure are shown as orange triangles, and those not reporting trauma exposure as green dots. Panel a shows the relationship on the linear additive scale, and panel b shows the relationship on the multiplicative scale. A significant interaction is observed on the additive scale only, as shown by differing slopes of the two regression lines in panel a.

See this image and copyright information in PMC

References

1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390: 1211–1259. - PMC - PubMed
1. McManus S, Bebbington P, Jenkins R, Brugha T. Mental Health and Wellbeing in England: Adult Psychiatric Morbidity Survey 2014: a Survey Carried Out for NHS Digital by NatCen Social Research and the Department of Health Sciences, University of Leicester. NHS Digital, 2016.
1. Green JG, McLaughlin KA, Berglund PA, Gruber MJ, Sampson NA, Zaslavsky AM et al. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry 2010; 67: 113–123. - PMC - PubMed
1. Nanni V, Uher R, Danese A. Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. Am J Psychiatry 2012; 169: 141–151. - PubMed
1. Kessler RC. The effects of stressful life events on depression. Annu Rev Psychol 1997; 48: 191–214. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources