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

Jonathan R I Coleman; Gerome Breen; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; A. Abdellaoui; C.V. Dolan; Jouke Jan  Hottenga; Hamdi Mbarek; C.M. Middeldorp; Michel G. Nivard; Gonneke Willemsen; D.I. Boomsma; Eco J.C. de Geus; A.T.F. Beekman; Rick Jansen; Yuri Milaneschi; Johannes H. Smit; Brenda W J H Penninx; Danielle Posthuma

doi:10.1038/s41380-019-0546-6

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

Jonathan R I Coleman
, Gerome Breen
, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
, A. Abdellaoui
, C.V. Dolan
, Jouke Jan Hottenga
, Hamdi Mbarek
, C.M. Middeldorp
, Michel G. Nivard
, Gonneke Willemsen
, D.I. Boomsma
, Eco J.C. de Geus
, A.T.F. Beekman
, Rick Jansen
, Yuri Milaneschi
, Johannes H. Smit
, Brenda W J H Penninx
, Danielle Posthuma

Research output: Contribution to Journal › Article › Academic › peer-review

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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 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.

Original language	English
Pages (from-to)	1430-1446
Number of pages	17
Journal	Molecular Psychiatry
Volume	25
Issue number	7
Early online date	23 Jan 2020
DOIs	https://doi.org/10.1038/s41380-019-0546-6
Publication status	Published - Jul 2020

Funding

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\u2019s 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).

Funders	Funder number
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
National Institute for Health Research
Maudsley Charity
National Institute for Health and Care Research
South London and Maudsley NHS Foundation Trust
National Institute on Drug Abuse
King's College London
National Health and Medical Research Council	1078901, 1087889
Alexander von Humboldt-Stiftung
National Institute of Mental Health	U01MH109528, T32MH017119, U01MH109514, U01MH109532
GSTT	TR130505
NWO	91619152
Medical Research Council	MC_PC_17228, MR/N015746/1, MC_PC_12028

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Netherlands Twin Register (NTR)

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Genomewide geneenvironment analyses of major depressive disorder and reported lifetime traumatic experiences in UK BiobankFinal published version, 1.89 MBLicence: Article 25fa Dutch Copyright Act

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Coleman, J. R. I., Breen, G., Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Abdellaoui, A., Dolan, C. V., Hottenga, J. J., Mbarek, H., Middeldorp, C. M., Nivard, M. G., Willemsen, G., Boomsma, D. I., de Geus, E. J. C., Beekman, A. T. F., Jansen, R., Milaneschi, Y., Smit, J. H., W J H Penninx, B., & Posthuma, D. (2020). Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank. Molecular Psychiatry, 25(7), 1430-1446. https://doi.org/10.1038/s41380-019-0546-6

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Coleman, JRI, Breen, G, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Abdellaoui, A, Dolan, CV, Hottenga, JJ, Mbarek, H, Middeldorp, CM, Nivard, MG, Willemsen, G, Boomsma, DI , de Geus, EJC, Beekman, ATF, Jansen, R, Milaneschi, Y, Smit, JH, W J H Penninx, B & Posthuma, D 2020, 'Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank', Molecular Psychiatry, vol. 25, no. 7, pp. 1430-1446. https://doi.org/10.1038/s41380-019-0546-6

Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank. / Coleman, Jonathan R I; Breen, Gerome; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium et al.
In: Molecular Psychiatry, Vol. 25, No. 7, 07.2020, p. 1430-1446.

Research output: Contribution to Journal › Article › Academic › peer-review

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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

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