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

View ORCID ProfileJonathan R.I. Coleman, Wouter J. Peyrot, View ORCID ProfileKirstin L. Purves, View ORCID ProfileKatrina A.S. Davis, Christopher Rayner, View ORCID ProfileShing Wan Choi, View ORCID ProfileChristopher Hübel, View ORCID ProfileHéléna A. Gaspar, View ORCID ProfileCarol Kan, View ORCID ProfileSandra Van der Auwera, View ORCID ProfileMark James Adams, View ORCID ProfileDonald M. Lyall, Karmel W. Choi, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, View ORCID ProfileErin C. Dunn, View ORCID ProfileEvangelos Vassos, View ORCID ProfileAndrea Danese, Barbara Maughan, View ORCID ProfileHans J. Grabe, View ORCID ProfileCathryn M. Lewis, View ORCID ProfilePaul F. O’Reilly, View ORCID ProfileAndrew M. McIntosh, View ORCID ProfileDaniel J. Smith, View ORCID ProfileNaomi R. Wray, View ORCID ProfileMatthew Hotopf, View ORCID ProfileThalia C. Eley, View ORCID ProfileGerome Breen
doi: https://doi.org/10.1101/247353
Jonathan R.I. Coleman
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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Wouter J. Peyrot
3Amsterdam UMC, Vrije Universiteit Medical Center, Department of Psychiatry, Amsterdam, The Netherlands
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Kirstin L. Purves
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Katrina A.S. Davis
2NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
4Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Christopher Rayner
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Shing Wan Choi
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Christopher Hübel
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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Héléna A. Gaspar
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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Carol Kan
4Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Sandra Van der Auwera
5Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
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Mark James Adams
6Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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Donald M. Lyall
7Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
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Karmel W. Choi
8Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
9Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
10Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, MA, USA
11Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
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12Consortium members listed in Supplementary Materials
Erin C. Dunn
10Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, MA, USA
11Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
13Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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Evangelos Vassos
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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Andrea Danese
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
14Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
15National and Specialist CAMHS Trauma and Anxiety Clinic, South London and Maudsley NHS Foundation Trust, London, UK
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Barbara Maughan
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Hans J. Grabe
5Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
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Cathryn M. Lewis
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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Paul F. O’Reilly
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Andrew M. McIntosh
6Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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Daniel J. Smith
7Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
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Naomi R. Wray
16Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
17Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia
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Matthew Hotopf
2NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
4Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Thalia C. Eley
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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  • For correspondence: gerome.breen@kcl.ac.uk thalia.eley@kcl.ac.uk
Gerome Breen
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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  • For correspondence: gerome.breen@kcl.ac.uk thalia.eley@kcl.ac.uk
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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 between individuals reporting and not reporting trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD was greater in participants reporting trauma exposure (24%) than in individuals not reporting trauma exposure (12%), taking into account the strong, positive genetic correlation observed between MDD and reported trauma exposure. 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 additional risk factors are present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

Footnotes

  • - Inclusion of additional sensitivity analyses increasing/decreasing the threshold for defining reported trauma exposure, and focussing on traumas experienced in childhood. No qualitative alterations to overall result. - Alteration to multiple-testing correction for genetic correlation analyses to better account for correlated phenotypes - Expanded discussion of potential mechanisms of observed increase in MDD SNP-based heritability when trauma exposure is reported - Substantial rewrite to increase clarity

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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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, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 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
bioRxiv 247353; doi: https://doi.org/10.1101/247353
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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, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 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
bioRxiv 247353; doi: https://doi.org/10.1101/247353

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