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

• DOI: 10.1038/s41380-019-0546-6
• Publication Date: 2020-01-23T02:02:49Z
• Authors: Jonathan R. I. Co...; 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 Au...; 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 Butte...; Jonas Bybjerg-Gra...; Na Cai; Enrique Castelao; Jane Hvarregaard ...; Toni-Kim Clarke; Jonathan R I Coleman; Lucía Colodro-Conde; Baptiste Couvy-Du...; 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-...; Farnush Farhadi H...; 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 ...; 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. Kretzsc...; 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 Middel...; 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 Pe...; Marianne Giørtz P...; 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 Thorge...; Matthew Traylor; Jens Treutlein; Vassily Trubetskoy; Andrés G Uitterli...; Daniel Umbricht; Sandra Van der Au...; Albert M van Hemert; Alexander Viktorin; Peter M Visscher; Yunpeng Wang; Bradley T. Webb; Shantel Marie Wei...; 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-My...; Merete Nordentoft; Markus M Nöthen; Michael C O’Donovan; Sara A Paciga; Nancy L Pedersen; Brenda W. J. H Pe...; 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
• Keywords: Netherlands Twin Register (NTR); Adult; Male; SYMPTOMS; Databases, Factual; 2804 Cellular and Molecular Neuroscience; 150; 610; Depressive Disorder, Major/epidemiology; Psychological Trauma; CHILDHOOD MALTREATMENT; Article; EVENTS; Databases; Cellular and Molecular Neuroscience; SDG 3 - Good Health and Well-being; 2738 Psychiatry and Mental health; ADVERSITY; 1312 Molecular Biology; Genetics; Humans; Psychological Trauma/epidemiology; Genetic Predisposition to Disease; Molecular Biology; Factual; Aged; RISK; Depressive Disorder; Depressive Disorder, Major; United Kingdom/epidemiology; Depression; HERITABILITY; Genetic Predisposition to Disease/genetics; PSYCHIATRIC-DISORDERS; Major; Middle Aged; United Kingdom; 3. Good health; Psychiatry and Mental health; ASSOCIATION ANALYSIS; BIOLOGICAL INSIGHTS; Female; Gene-Environment Interaction; Self Report; Waist Circumference; on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; MENTAL-HEALTH; Genome-Wide Association Study

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.