Genetic and environmental determinants of stressful life events and their overlap with depression and neuroticism
Mark J Adams,
David M Howard,
Aleix Arnau Soler,
Pippa A. Thomson,
Blair H Smith,
Lynne J. Hocking,
Lynsey S. Hall,
David J. Porteous,
Ian J Deary,
Andrew M McIntosh
Posted 31 Oct 2017
bioRxiv DOI: 10.1101/211896 (published DOI: 10.12688/wellcomeopenres.13893.1)
Posted 31 Oct 2017
Background: Stressful life events (SLEs) and neuroticism are risk factors for major depressive disorder (MDD). However, SLEs and neuroticism are heritable traits that are correlated with genetic risk for MDD. In the current study, we sought to investigate the genetic and environmental contributions to SLEs in a large family-based sample, and quantify any genetic overlap with MDD and neuroticism. Methods: A subset of Generation Scotland: the Scottish Family Health Study, consisting of 9618 individuals comprise the present study. We estimated the heritability of SLEs using pedigree-based and molecular genetic data. The environment was assessed by modelling familial, couple and sibling components. Using polygenic risk scores (PRS) and LD score regression we analysed the genetic overlap between MDD, neuroticism and SLEs. Results: Past 6-month life events were positively correlated with lifetime MDD status (β=0.21, r2=1.1%, p=2.5 x 10-25) and neuroticism (β=0.13, r2=1.9%, p=1.04 x 10-37). Common SNPs explained 8% of the variance in personal life events (those directly affecting the individual) (S.E.=0.03, p=9 x 10-4). A significant effect of couple environment accounted for 13% (S.E.=0.03, p=0.016) of variation in SLEs. PRS analyses found that individuals with higher PRS for MDD reported more SLEs (β=0.05, r2=0.3%, p=3 x 10-5). LD score regression demonstrated genetic correlations between MDD and both SLEs (rG=0.33, S.E.=0.08 ) and neuroticism (rG=0.15, S.E.=0.07). Conclusions: These findings suggest that SLEs are partially heritable and this heritability is shared with risk for MDD and neuroticism. Further work should determine the causal direction and source of these associations.
- Downloaded 408 times
- Download rankings, all-time:
- Site-wide: 58,592
- In genetics: 2,815
- Year to date:
- Site-wide: 122,247
- Since beginning of last month:
- Site-wide: 98,638
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!