Genome-wide by environment interaction study of stressful life events and hospital-treated depression in the iPSYCH2012 sample

Abstract Background Researchers have long investigated a hypothesized interaction between genetic risk and stressful life events in the etiology of depression, but studies on the topic have yielded inconsistent results. Methods We conducted a genome-wide environment interaction study in 18,532 patients with depression from hospital-based settings and 20,184 population controls. All individuals were drawn from the iPSYCH2012 case-cohort study, a nationally representative sample identified from Danish national registers. Information on stressful life events including family disruption, serious medical illness, death of a first-degree relative, parental disability and child maltreatment were identified from the registers and operationalized as a time-varying count variable. Hazard ratios for main and interaction effects were estimated using Cox regressions weighted to accommodate the case-cohort design. Our replication sample included 22,880 depression cases and 50,378 controls from the UK Biobank. Results The GWEIS in the iPSYCH2012 sample yielded three novel, genome-wide significant (P Conclusions In this large, population-based GWEIS we did not find any replicable hits for interaction. Future gene-by-stress research in depression should focus on establishing even larger collaborative genome-wide environment interaction studies to attain sufficient power.