TY - JOUR
T1 - A validation of the diathesis-stress model for depression in Generation Scotland
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
AU - Arnau-Soler, Aleix
AU - Adams, Mark J.
AU - Clarke, Toni-Kim
AU - MacIntyre, Donald J.
AU - Milburn, Keith
AU - Navrady, Lauren
AU - Hayward, Caroline
AU - McIntosh, Andrew
AU - Thomson, Pippa A.
N1 - 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).
PY - 2019/1/18
Y1 - 2019/1/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85060143369&partnerID=8YFLogxK
U2 - 10.1038/s41398-018-0356-7
DO - 10.1038/s41398-018-0356-7
M3 - Article
C2 - 30659167
VL - 9
SP - 1
EP - 10
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
IS - 1
M1 - 25
ER -