Genetic and environmental determinants of stressful life events and their overlap with depression and neuroticism

• DOI: 10.12688/wellcomeopenres.13893.1
• Publication Date: 2018-02-14T09:40:58Z
• Authors: Toni-Kim Clarke; Yanni Zeng; Lauren Navrady; Charley Xia; Chris Haley; Archie Campbell; Pau Navarro; Carmen Amador; Mark J. Adams; David M. Howard; Aleix Soler; Caroline Hayward; Pippa A. Thomson; Blair H. Smith; Sandosh Padmanabhan; Lynne J. Hocking; Lynsey S. Hall; David J. Porteous; ; Ian J. Deary; Andrew M. McIntosh
• Keywords: Neuroticism; 0303 health sciences; 03 medical and health sciences; Depression; Genetics; 610; 600; Stress; Research Article; 3. Good health

<ns4:p><ns4:bold>Background: </ns4:bold>Stressful life events (SLEs) and neuroticism are risk factors for major depressive disorder (MDD). However, SLEs heritable genetic is correlated with MDD. We sought to investigate the environmental contributions in a family-based sample, quantify overlap MDD neuroticism.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> A subset of Generation Scotland: Scottish Family Health Study (GS), consisting 9618 individuals information on MDD, past 6 month SLEs, genome-wide genotype data was used present study. estimated heritability using GCTA software. The contribution assessed by modelling familial, couple sibling components. Using polygenic scores (PRS) LD score regression (LDSC) we analysed between SLEs.</ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> Past 6-month were positively lifetime status (β=0.21, r<ns4:sup>2</ns4:sup>=1.1%, p=2.5 x 10<ns4:sup>-25</ns4:sup>) (β =0.13, r<ns4:sup>2</ns4:sup>=1.9%, p=1.04 10<ns4:sup>-37</ns4:sup>) at phenotypic level. Common SNPs explained 8% variance personal (those directly affecting individual) (S.E.=0.03, p= 9 10<ns4:sup>-4</ns4:sup>). significant effect environment detected accounting 13% p=0.016) variation SLEs. PRS analyses found that reporting more associated higher =0.05, r<ns4:sup>2</ns4:sup>=0.3%, p=3 10<ns4:sup>-5</ns4:sup>), but not neuroticism. LDSC showed correlation both (r<ns4:sub>G</ns4:sub>=0.33, S.E.=0.08 ) (r<ns4:sub>G</ns4:sub>=0.15, S.E.=0.07).</ns4:p><ns4:p> <ns4:bold>Conclusions:</ns4:bold> These findings suggest should be regarded solely as they partially this shared Further work needed determine causal direction source these associations.</ns4:p>