A validation of the diathesis-stress model for depression in Generation Scotland

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Aleix Arnau-Soler; Mark J. Adams; Toni-Kim Clarke; Donald J. MacIntyre; Keith Milburn; Lauren Navrady; Caroline Hayward; Andrew McIntosh; Pippa A. Thomson

doi:10.1038/s41398-018-0356-7

A validation of the diathesis-stress model for depression in Generation Scotland

, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Aleix Arnau-Soler (Lead / Corresponding author), Mark J. Adams, Toni-Kim Clarke, Donald J. MacIntyre, Keith Milburn, Lauren Navrady, Caroline Hayward, Andrew McIntosh, Pippa A. Thomson (Lead / Corresponding author)

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Abstract

Depression has well-established influences from genetic and environmental risk factors. This has led to the diathesis-stress theory, which assumes a multiplicative gene-by-environment interaction (GxE) effect on risk. Recently, Colodro-Conde et al. empirically tested this theory, using the polygenic risk score for major depressive disorder (PRS, genes) and stressful life events (SLE, environment) effects on depressive symptoms, identifying significant GxE effects with an additive contribution to liability. We have tested the diathesis-stress theory on an independent sample of 4919 individuals. We identified nominally significant positive GxE effects in the full cohort (R2 = 0.08%, p = 0.049) and in women (R2 = 0.19%, p = 0.017), but not in men (R2 = 0.15%, p = 0.07). GxE effects were nominally significant, but only in women, when SLE were split into those in which the respondent plays an active or passive role (R2 = 0.15%, p = 0.038; R2 = 0.16%, p = 0.033, respectively). High PRS increased the risk of depression in participants reporting high numbers of SLE (p = 2.86 × 10-4). However, in those participants who reported no recent SLE, a higher PRS appeared to increase the risk of depressive symptoms in men (β = 0.082, p = 0.016) but had a protective effect in women (β = -0.061, p = 0.037). This difference was nominally significant (p = 0.017). Our study reinforces the evidence of additional risk in the aetiology of depression due to GxE effects. However, larger sample sizes are required to robustly validate these findings.

Original language	English
Article number	25
Pages (from-to)	1-10
Number of pages	10
Journal	Translational Psychiatry
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41398-018-0356-7
Publication status	Published - 18 Jan 2019

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, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Arnau-Soler, A., Adams, M. J., Clarke, T-K., MacIntyre, D. J., Milburn, K., Navrady, L., Hayward, C., & McIntosh, A., & Thomson, P. A. (2019). A validation of the diathesis-stress model for depression in Generation Scotland. Translational Psychiatry, 9(1), 1-10. [25]. https://doi.org/10.1038/s41398-018-0356-7

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ; Arnau-Soler, Aleix ; Adams, Mark J. ; Clarke, Toni-Kim ; MacIntyre, Donald J. ; Milburn, Keith ; Navrady, Lauren ; Hayward, Caroline ; McIntosh, Andrew ; Thomson, Pippa A. / A validation of the diathesis-stress model for depression in Generation Scotland. In: Translational Psychiatry. 2019 ; Vol. 9, No. 1. pp. 1-10.

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abstract = "Depression has well-established influences from genetic and environmental risk factors. This has led to the diathesis-stress theory, which assumes a multiplicative gene-by-environment interaction (GxE) effect on risk. Recently, Colodro-Conde et al. empirically tested this theory, using the polygenic risk score for major depressive disorder (PRS, genes) and stressful life events (SLE, environment) effects on depressive symptoms, identifying significant GxE effects with an additive contribution to liability. We have tested the diathesis-stress theory on an independent sample of 4919 individuals. We identified nominally significant positive GxE effects in the full cohort (R2 = 0.08%, p = 0.049) and in women (R2 = 0.19%, p = 0.017), but not in men (R2 = 0.15%, p = 0.07). GxE effects were nominally significant, but only in women, when SLE were split into those in which the respondent plays an active or passive role (R2 = 0.15%, p = 0.038; R2 = 0.16%, p = 0.033, respectively). High PRS increased the risk of depression in participants reporting high numbers of SLE (p = 2.86 × 10-4). However, in those participants who reported no recent SLE, a higher PRS appeared to increase the risk of depressive symptoms in men (β = 0.082, p = 0.016) but had a protective effect in women (β = -0.061, p = 0.037). This difference was nominally significant (p = 0.017). Our study reinforces the evidence of additional risk in the aetiology of depression due to GxE effects. However, larger sample sizes are required to robustly validate these findings.",

author = "Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium and Aleix Arnau-Soler and Adams, {Mark J.} and Toni-Kim Clarke and MacIntyre, {Donald J.} and Keith Milburn and Lauren Navrady and Caroline Hayward and Andrew McIntosh and Thomson, {Pippa A.}",

note = "A.A.S. is funded by the University of Edinburgh (www.ed.ac.uk) and MRC for his PhD study at the University of Edinburgh Institute of Genetics and Molecular Medicine (www.ed.ac.uk/igmm). D.J.M. acknowledges the financial support of NHS Research Scotland (NRS) through NHS Lothian. MA is supported by STRADL through a Wellcome Trust Strategic Award (reference 104036/Z/14/Z). Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. The genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z).",

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Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Arnau-Soler, A, Adams, MJ, Clarke, T-K, MacIntyre, DJ, Milburn, K, Navrady, L, Hayward, C & McIntosh, A & Thomson, PA 2019, 'A validation of the diathesis-stress model for depression in Generation Scotland', Translational Psychiatry, vol. 9, no. 1, 25, pp. 1-10. https://doi.org/10.1038/s41398-018-0356-7

A validation of the diathesis-stress model for depression in Generation Scotland. /; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Arnau-Soler, Aleix (Lead / Corresponding author); Adams, Mark J.; Clarke, Toni-Kim; MacIntyre, Donald J.; Milburn, Keith; Navrady, Lauren; Hayward, Caroline; McIntosh, Andrew; Thomson, Pippa A. (Lead / Corresponding author).

In: Translational Psychiatry, Vol. 9, No. 1, 25, 18.01.2019, p. 1-10.

Research output: Contribution to journal › Article

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AU - Adams, Mark J.

AU - Clarke, Toni-Kim

AU - MacIntyre, Donald J.

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AU - Hayward, Caroline

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AU - Thomson, Pippa A.

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