Jonathan R. I. Coleman, Wouter J. Peyrot, Kirstin Purves, Katrina A. S. Davis, Christopher Rayner, Shing Wan Choi, Christopher Huebel, Héléna A. Gaspar, Carol Kan, Sandra Van der Auwera, Mark J. Adams, Donald Lyall, Karmel W. Choi, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Erin C. Dunn, Evangelos Vassos, Andrea Danese, Barbara Maughan, H. J. Grabe, Cathryn M. Lewis & 7 more Paul F. O'Reilly, Andrew M. McIntosh, Daniel J Smith, Naomi R. Wray, Matthew Hotopf, Thalia C. Eley, Gerome Breen
| Original language | English |
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| Journal | Molecular Psychiatry |
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| Early online date | 23 Jan 2020 |
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| DOIs | |
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| Publication status | Published - 23 Jan 2020 |
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- Jonathan R. I. Coleman (NIHR Maudsley Biomedical Research Centre, Social Genetic & Developmental Psychiatry)
- Kirstin Purves (Social Genetic & Developmental Psychiatry)
- Katrina A. S. Davis (Psychological Medicine, NIHR Maudsley Biomedical Research Centre)
- Christopher Rayner (Social Genetic & Developmental Psychiatry)
- Shing Wan Choi
- Christopher Huebel (Social Genetic & Developmental Psychiatry)
- Héléna A. Gaspar (NIHR Maudsley Biomedical Research Centre, Social Genetic & Developmental Psychiatry)
- Carol Kan (Psychological Medicine)
- Evangelos Vassos (NIHR Maudsley Biomedical Research Centre, Social Genetic & Developmental Psychiatry)
- Andrea Danese (Social Genetic & Developmental Psychiatry, Child and Adolescent Mental Health Clinical Academic Group, Child & Adolescent Psychiatry)
- Cathryn M. Lewis (Medical & Molecular Genetics, NIHR Maudsley Biomedical Research Centre, Social Genetic & Developmental Psychiatry)
- Paul F. O'Reilly (Social Genetic & Developmental Psychiatry)
- Matthew Hotopf (Psychological Medicine, Psychological Medicine and Integrated Care Clinical Academic Group, Psychosis Clinical Academic Group, NIHR Maudsley Biomedical Research Centre)
- Thalia C. Eley (Social Genetic & Developmental Psychiatry, NIHR Maudsley Biomedical Research Centre)
- Gerome Breen (Social Genetic & Developmental Psychiatry, NIHR Maudsley Biomedical Research Centre)
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 = 1.8x10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3x10-4). 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.