Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland

Overview of the analyses conducted in this study: (i) identify loci associated with depressive symptoms through genetic response to SLE; (ii) test whether results of studying dependent and independent SLE support a contribution of genetically mediated exposure to stress; (iii) assess whether GxE effects improve the proportion of phenotypic variance in depressive symptoms explained by genetic additive main effects alone and (iv) test whether there is significant overlap in the genetic aetiology of the response to SLE and mental and physical stress-related phenotypes. Two core cohorts are used, Generation Scotland (GS) and UK Biobank (UKB). Summary statistics from genome-wide association studies (GWAS) and genome-wide by environment interaction studies (GWEIS) are used to generate polygenic risk scores (PRSs). Summary statistics from Psychiatric Genetic Consortium (PGC) Major Depressive Disorder (MDD) GWAS are also used to generate PRS (PRSMDD). PRS weighted by: additive effects (PRSD and PRSMDD), GxE effects (PRSGxE) and joint effects (the combined additive and GxE effect; PRSJoint), are used for phenotypic prediction. TSLE stands for total number of SLE reported. DSLE stands for SLE dependent on an individual’s own behaviour. Conversely, ISLE stands for independent SLE. N stands for sample size. NnoGS stands for sample size with GS individuals removed. NnoUKB stands for sample size with UKB individuals remove