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

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1038/s41380-019-0546-6

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

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Medicine

Résultat de recherche: Article › examen par les pairs

111 Citations (Scopus)

Résumé

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.

Langue d'origine	English
Pages (de-à)	1430-1446
Nombre de pages	17
Journal	Molecular Psychiatry
Volume	25
Numéro de publication	7
DOI	https://doi.org/10.1038/s41380-019-0546-6
Statut de publication	Published - juill. 1 2020

Note bibliographique

Funding Information:
Acknowledgements We thank the members of the UK Biobank Mental Health Genetics Group for their valuable discussion and feedback on this work. We are also deeply indebted to the scientists involved in the construction of the UK Biobank, and to the investigators who comprise the PGC. Finally, we thank the hundreds of thousands of subjects who have shared their life experiences with investigators in the UK Biobank and the PGC. This research has been conducted using the UK Biobank Resource, as an approved extension to application 16577 (Dr Breen). This study represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). WJP was funded by NWO Veni grant 91619152. KLP acknowledges funding from the Alexander von Humboldt Foundation. KWC was funded in part by the National Institute of Mental Health (T32MH017119). NRW acknowledges funding from the Australian National Health and Medical Research Council (1078901 and 1087889). PGC has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (U01 MH109528 and U01 MH1095320).

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

ASJC Scopus Subject Areas

Molecular Biology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

ODD de l’ONU

Cette action contribue à la réalisation des objectifs de développement durable suivants

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10.1038/s41380-019-0546-6

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

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.",

author = "{Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Coleman, {Jonathan R.I.} and Peyrot, {Wouter J.} and Purves, {Kirstin L.} and Davis, {Katrina A.S.} and Christopher Rayner and Choi, {Shing Wan} and Christopher H{\"u}bel and Gaspar, {H{\'e}l{\'e}na A.} and Carol Kan and {Van der Auwera}, Sandra and Adams, {Mark James} and Lyall, {Donald M.} and Choi, {Karmel W.} and Wray, {Naomi R.} and Stephan Ripke and Manuel Mattheisen and Maciej Trzaskowski and Byrne, {Enda M.} and Abdel Abdellaoui and Esben Agerbo and Air, {Tracy M.} and Andlauer, {Till F.M.} and Bacanu, {Silviu Alin} and Marie B{\ae}kvad-Hansen and Beekman, {Aartjan T.F.} and Bigdeli, {Tim B.} and Binder, {Elisabeth B.} and Julien Bryois and Buttensch{\o}n, {Henriette N.} and Jonas Bybjerg-Grauholm and Na Cai and Enrique Castelao and Christensen, {Jane Hvarregaard} and Clarke, {Toni Kim} and Luc{\'i}a Colodro-Conde and Baptiste Couvy-Duchesne and Nick Craddock and Crawford, {Gregory E.} and Gail Davies and Deary, {Ian J.} and Franziska Degenhardt and Derks, {Eske M.} and Nese Direk and Dolan, {Conor V.} and Dunn, {Erin C.} and Eley, {Thalia C.} and Valentina Escott-Price and Kiadeh, {Farnush Farhadi Hassan} and Finucane, {Hilary K.} and Rudolf Uher",

note = "Funding Information: Acknowledgements We thank the members of the UK Biobank Mental Health Genetics Group for their valuable discussion and feedback on this work. We are also deeply indebted to the scientists involved in the construction of the UK Biobank, and to the investigators who comprise the PGC. Finally, we thank the hundreds of thousands of subjects who have shared their life experiences with investigators in the UK Biobank and the PGC. This research has been conducted using the UK Biobank Resource, as an approved extension to application 16577 (Dr Breen). This study represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). WJP was funded by NWO Veni grant 91619152. KLP acknowledges funding from the Alexander von Humboldt Foundation. KWC was funded in part by the National Institute of Mental Health (T32MH017119). NRW acknowledges funding from the Australian National Health and Medical Research Council (1078901 and 1087889). PGC has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (U01 MH109528 and U01 MH1095320). Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2020",

month = jul,

day = "1",

doi = "10.1038/s41380-019-0546-6",

language = "English",

volume = "25",

pages = "1430--1446",

journal = "Molecular Psychiatry",

issn = "1359-4184",

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number = "7",

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TY - JOUR

T1 - Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

AU - Coleman, Jonathan R.I.

AU - Peyrot, Wouter J.

AU - Purves, Kirstin L.

AU - Davis, Katrina A.S.

AU - Rayner, Christopher

AU - Choi, Shing Wan

AU - Hübel, Christopher

AU - Gaspar, Héléna A.

AU - Kan, Carol

AU - Van der Auwera, Sandra

AU - Adams, Mark James

AU - Lyall, Donald M.

AU - Choi, Karmel W.

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till F.M.

AU - Bacanu, Silviu Alin

AU - Bækvad-Hansen, Marie

AU - Beekman, Aartjan T.F.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Bryois, Julien

AU - Buttenschøn, Henriette N.

AU - Bybjerg-Grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

AU - Clarke, Toni Kim

AU - Colodro-Conde, Lucía

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Davies, Gail

AU - Deary, Ian J.

AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - Direk, Nese

AU - Dolan, Conor V.

AU - Dunn, Erin C.

AU - Eley, Thalia C.

AU - Escott-Price, Valentina

AU - Kiadeh, Farnush Farhadi Hassan

AU - Finucane, Hilary K.

AU - Uher, Rudolf

N1 - Funding Information: Acknowledgements We thank the members of the UK Biobank Mental Health Genetics Group for their valuable discussion and feedback on this work. We are also deeply indebted to the scientists involved in the construction of the UK Biobank, and to the investigators who comprise the PGC. Finally, we thank the hundreds of thousands of subjects who have shared their life experiences with investigators in the UK Biobank and the PGC. This research has been conducted using the UK Biobank Resource, as an approved extension to application 16577 (Dr Breen). This study represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). WJP was funded by NWO Veni grant 91619152. KLP acknowledges funding from the Alexander von Humboldt Foundation. KWC was funded in part by the National Institute of Mental Health (T32MH017119). NRW acknowledges funding from the Australian National Health and Medical Research Council (1078901 and 1087889). PGC has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (U01 MH109528 and U01 MH1095320). Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2020/7/1

Y1 - 2020/7/1

N2 - 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.

AB - 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.

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

Résumé

Note bibliographique

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