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Journal Articles Molecular Psychiatry Year : 2020

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

Jonathan Coleman (1) , Wouter Peyrot , Kirstin Purves , Katrina Davis , Christopher Rayner (2, 3, 4) , Shing Wan Choi , Christopher Hübel (5, 6) , Héléna Gaspar (6) , Carol Kan , Sandra van der Auwera , Mark James Adams (7) , Donald Lyall , Karmel Choi (8, 9, 10) , Naomi Wray (11) , Stephan Ripke (10, 12) , Manuel Mattheisen (13, 14, 15, 16) , Maciej Trzaskowski , Enda Byrne (17) , Abdel Abdellaoui , Mark Adams (18, 3) , Esben Agerbo , Tracy Air , Till Andlauer , Silviu-Alin Bacanu , Marie Bækvad-Hansen , Aartjan Beekman , Tim Bigdeli , Elisabeth Binder , Julien Bryois , Henriette Buttenschøn , Jonas Bybjerg-Grauholm , Na Cai , Enrique Castelao , Jane Hvarregaard Christensen , Toni-Kim Clarke , Jonathan Coleman , Lucía Colodro-Conde , Baptiste Couvy-Duchesne (19) , Nick Craddock , Gregory Crawford , Gail Davies , Ian Deary , Franziska Degenhardt , Eske Derks , Nese Direk , Conor Dolan , Erin Dunn , Thalia Eley , Valentina Escott-Price , Farnush Farhadi Hassan Kiadeh , Hilary Finucane , Jerome Foo , Andreas Forstner , Josef Frank , Héléna Gaspar , Michael Gill , Fernando Goes , Scott Gordon , Jakob Grove , Lynsey Hall , Christine Søholm Hansen , Thomas Hansen , Stefan Herms , Ian Hickie , Per Hoffmann , Georg Homuth , Carsten Horn , Jouke-Jan Hottenga , David Hougaard , David Howard , Marcus Ising , Rick Jansen , Ian Jones , Lisa Jones , Eric Jorgenson , James Knowles , Isaac Kohane , Julia Kraft , Warren Kretzschmar , Zoltán Kutalik , Yihan Li , Penelope Lind , Donald Macintyre , Dean Mackinnon , Robert Maier , Wolfgang Maier , Jonathan Marchini , Hamdi Mbarek , Patrick Mcgrath , Peter Mcguffin , Sarah Medland , Divya Mehta , Christel Middeldorp , Evelin Mihailov , Yuri Milaneschi , Lili Milani , Francis Mondimore , Grant Montgomery , Sara Mostafavi , Niamh Mullins , Matthias Nauck , Bernard Ng , Michel Nivard , Dale Nyholt , Paul O’reilly , Hogni Oskarsson , Michael Owen , Jodie Painter , Carsten Bøcker Pedersen , Marianne Giørtz Pedersen , Roseann Peterson , Erik Pettersson , Wouter Peyrot , Giorgio Pistis , Danielle Posthuma , Jorge Quiroz , Per Qvist , John Rice , Brien Riley , Margarita Rivera , Saira Saeed Mirza , Robert Schoevers , Eva Schulte , Ling Shen , Jianxin Shi , Stanley Shyn , Engilbert Sigurdsson , Grant Sinnamon , Johannes Smit , Daniel Smith , Hreinn Stefansson , Stacy Steinberg , Fabian Streit , Jana Strohmaier , Katherine Tansey , Henning Teismann , Alexander Teumer , Wesley Thompson , Pippa Thomson , Thorgeir Thorgeirsson , Matthew Traylor , Jens Treutlein , Vassily Trubetskoy , Andrés Uitterlinden , Daniel Umbricht , Sandra van der Auwera , Albert van Hemert , Alexander Viktorin , Peter Visscher , Yunpeng Wang , Bradley Webb , Shantel Marie Weinsheimer , Jürgen Wellmann , Gonneke Willemsen , Stephanie Witt , Yang Wu , Hualin Xi , Jian Yang , Futao Zhang , Volker Arolt , Bernhard Baune , Klaus Berger , Dorret Boomsma , Sven Cichon , Udo Dannlowski , E. de Geus , J Raymond Depaulo , Enrico Domenici , Katharina Domschke , Tõnu Esko , Hans Grabe , Steven Hamilton , Caroline Hayward , Andrew Heath , Kenneth Kendler , Stefan Kloiber , Glyn Lewis , Qingqin Li , Susanne Lucae , Pamela Madden , Patrik Magnusson , Nicholas Martin , Andrew McIntosh , Andres Metspalu , Ole Mors , Preben Bo Mortensen , Bertram Müller-Myhsok , Merete Nordentoft , Markus Nöthen , Michael O’donovan , Sara Paciga , Nancy Pedersen , Brenda Penninx , Roy Perlis , David Porteous , James Potash , Martin Preisig , Marcella Rietschel , Catherine Schaefer , Thomas Schulze , Jordan Smoller , Kari Stefansson , Henning Tiemeier , Rudolf Uher , Henry Völzke , Myrna Weissman , Thomas Werge , Cathryn Lewis , Douglas Levinson , Gerome Breen , Anders Børglum , Patrick Sullivan , Erin Dunn , Evangelos Vassos , Andrea Danese , Barbara Maughan , Hans Grabe , Cathryn Lewis , Paul O’reilly , Andrew McIntosh , Daniel Smith , Naomi Wray , Matthew Hotopf , Thalia Eley , Gerome Breen
Wouter Peyrot
  • Function : Author
Kirstin Purves
Katrina Davis
  • Function : Author
Shing Wan Choi
  • Function : Author
Carol Kan
Sandra van der Auwera
  • Function : Author
Mark James Adams
Donald Lyall
  • Function : Author
Maciej Trzaskowski
  • Function : Author
Abdel Abdellaoui
  • Function : Author
Esben Agerbo
  • Function : Author
Tracy Air
  • Function : Author
Till Andlauer
  • Function : Author
Silviu-Alin Bacanu
  • Function : Author
Marie Bækvad-Hansen
  • Function : Author
Aartjan Beekman
  • Function : Author
Tim Bigdeli
  • Function : Author
Elisabeth Binder
  • Function : Author
Julien Bryois
  • Function : Author
Henriette Buttenschøn
  • Function : Author
Jonas Bybjerg-Grauholm
  • Function : Author
Na Cai
  • Function : Author
Enrique Castelao
  • Function : Author
Jane Hvarregaard Christensen
  • Function : Author
Toni-Kim Clarke
  • Function : Author
Jonathan Coleman
  • Function : Author
Lucía Colodro-Conde
  • Function : Author
Nick Craddock
  • Function : Author
Gregory Crawford
  • Function : Author
Gail Davies
  • Function : Author
Ian Deary
  • Function : Author
Franziska Degenhardt
  • Function : Author
Eske Derks
  • Function : Author
Nese Direk
  • Function : Author
Conor Dolan
  • Function : Author
Erin Dunn
  • Function : Author
Thalia Eley
  • Function : Author
Valentina Escott-Price
  • Function : Author
Farnush Farhadi Hassan Kiadeh
  • Function : Author
Hilary Finucane
  • Function : Author
Jerome Foo
  • Function : Author
Andreas Forstner
  • Function : Author
Josef Frank
  • Function : Author
Héléna Gaspar
  • Function : Author
Michael Gill
  • Function : Author
Fernando Goes
  • Function : Author
Scott Gordon
  • Function : Author
Jakob Grove
  • Function : Author
Lynsey Hall
  • Function : Author
Christine Søholm Hansen
  • Function : Author
Thomas Hansen
  • Function : Author
Stefan Herms
  • Function : Author
Ian Hickie
  • Function : Author
Per Hoffmann
  • Function : Author
Georg Homuth
  • Function : Author
Carsten Horn
  • Function : Author
Jouke-Jan Hottenga
  • Function : Author
David Hougaard
  • Function : Author
David Howard
  • Function : Author
Marcus Ising
  • Function : Author
Rick Jansen
  • Function : Author
Ian Jones
  • Function : Author
Lisa Jones
  • Function : Author
Eric Jorgenson
  • Function : Author
James Knowles
  • Function : Author
Isaac Kohane
  • Function : Author
Julia Kraft
  • Function : Author
Warren Kretzschmar
  • Function : Author
Zoltán Kutalik
  • Function : Author
Yihan Li
  • Function : Author
Penelope Lind
  • Function : Author
Donald Macintyre
  • Function : Author
Dean Mackinnon
  • Function : Author
Robert Maier
  • Function : Author
Wolfgang Maier
  • Function : Author
Jonathan Marchini
  • Function : Author
Hamdi Mbarek
  • Function : Author
Patrick Mcgrath
  • Function : Author
Peter Mcguffin
  • Function : Author
Sarah Medland
  • Function : Author
Divya Mehta
  • Function : Author
Christel Middeldorp
  • Function : Author
Evelin Mihailov
  • Function : Author
Yuri Milaneschi
  • Function : Author
Lili Milani
  • Function : Author
Francis Mondimore
  • Function : Author
Grant Montgomery
  • Function : Author
Sara Mostafavi
  • Function : Author
Niamh Mullins
  • Function : Author
Matthias Nauck
  • Function : Author
Bernard Ng
  • Function : Author
Michel Nivard
  • Function : Author
Dale Nyholt
  • Function : Author
Paul O’reilly
  • Function : Author
Hogni Oskarsson
  • Function : Author
Michael Owen
  • Function : Author
Jodie Painter
  • Function : Author
Carsten Bøcker Pedersen
  • Function : Author
Marianne Giørtz Pedersen
  • Function : Author
Roseann Peterson
  • Function : Author
Erik Pettersson
  • Function : Author
Wouter Peyrot
  • Function : Author
Giorgio Pistis
  • Function : Author
Danielle Posthuma
  • Function : Author
Jorge Quiroz
  • Function : Author
Per Qvist
  • Function : Author
John Rice
  • Function : Author
Brien Riley
  • Function : Author
Margarita Rivera
  • Function : Author
Saira Saeed Mirza
  • Function : Author
Robert Schoevers
  • Function : Author
Eva Schulte
  • Function : Author
Ling Shen
  • Function : Author
Jianxin Shi
  • Function : Author
Stanley Shyn
  • Function : Author
Engilbert Sigurdsson
  • Function : Author
Grant Sinnamon
  • Function : Author
Johannes Smit
  • Function : Author
Daniel Smith
  • Function : Author
Hreinn Stefansson
  • Function : Author
Stacy Steinberg
  • Function : Author
Fabian Streit
  • Function : Author
Jana Strohmaier
  • Function : Author
Katherine Tansey
  • Function : Author
Henning Teismann
  • Function : Author
Alexander Teumer
  • Function : Author
Wesley Thompson
  • Function : Author
Pippa Thomson
  • Function : Author
Thorgeir Thorgeirsson
  • Function : Author
Matthew Traylor
  • Function : Author
Jens Treutlein
  • Function : Author
Vassily Trubetskoy
  • Function : Author
Andrés Uitterlinden
  • Function : Author
Daniel Umbricht
  • Function : Author
Sandra van der Auwera
  • Function : Author
Albert van Hemert
  • Function : Author
Alexander Viktorin
  • Function : Author
Peter Visscher
  • Function : Author
Yunpeng Wang
  • Function : Author
Bradley Webb
  • Function : Author
Shantel Marie Weinsheimer
  • Function : Author
Jürgen Wellmann
  • Function : Author
Gonneke Willemsen
  • Function : Author
Stephanie Witt
  • Function : Author
Yang Wu
  • Function : Author
Hualin Xi
  • Function : Author
Jian Yang
  • Function : Author
Futao Zhang
  • Function : Author
Volker Arolt
  • Function : Author
Bernhard Baune
  • Function : Author
Klaus Berger
  • Function : Author
Dorret Boomsma
  • Function : Author
Sven Cichon
  • Function : Author
Udo Dannlowski
  • Function : Author
E. de Geus
  • Function : Author
J Raymond Depaulo
  • Function : Author
Enrico Domenici
  • Function : Author
Katharina Domschke
  • Function : Author
Tõnu Esko
  • Function : Author
Hans Grabe
  • Function : Author
Steven Hamilton
  • Function : Author
Caroline Hayward
  • Function : Author
Andrew Heath
  • Function : Author
Kenneth Kendler
  • Function : Author
Stefan Kloiber
  • Function : Author
Glyn Lewis
  • Function : Author
Qingqin Li
  • Function : Author
Susanne Lucae
  • Function : Author
Pamela Madden
  • Function : Author
Patrik Magnusson
  • Function : Author
Nicholas Martin
  • Function : Author
Andrew McIntosh
  • Function : Author
Andres Metspalu
  • Function : Author
Ole Mors
  • Function : Author
Preben Bo Mortensen
  • Function : Author
Bertram Müller-Myhsok
  • Function : Author
Merete Nordentoft
  • Function : Author
Markus Nöthen
  • Function : Author
Michael O’donovan
  • Function : Author
Sara Paciga
  • Function : Author
Nancy Pedersen
  • Function : Author
Brenda Penninx
  • Function : Author
Roy Perlis
  • Function : Author
David Porteous
  • Function : Author
James Potash
  • Function : Author
Martin Preisig
  • Function : Author
Marcella Rietschel
  • Function : Author
Catherine Schaefer
  • Function : Author
Thomas Schulze
  • Function : Author
Jordan Smoller
  • Function : Author
Kari Stefansson
  • Function : Author
Henning Tiemeier
  • Function : Author
Rudolf Uher
  • Function : Author
Henry Völzke
  • Function : Author
Myrna Weissman
  • Function : Author
Thomas Werge
  • Function : Author
Cathryn Lewis
  • Function : Author
Douglas Levinson
  • Function : Author
Gerome Breen
  • Function : Author
Anders Børglum
  • Function : Author
Patrick Sullivan
  • Function : Author
Erin Dunn
Evangelos Vassos
Andrea Danese
Barbara Maughan
  • Function : Author
Hans Grabe
Cathryn Lewis
Paul O’reilly
Andrew McIntosh
Daniel Smith
Naomi Wray
Matthew Hotopf
  • Function : Author
Thalia Eley
Gerome Breen

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 (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.

Dates and versions

hal-04573350 , version 1 (13-05-2024)

Identifiers

Cite

Jonathan Coleman, Wouter Peyrot, Kirstin Purves, Katrina Davis, Christopher Rayner, et al.. Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank. Molecular Psychiatry, 2020, 25 (7), pp.1430-1446. ⟨10.1038/s41380-019-0546-6⟩. ⟨hal-04573350⟩
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