Abstract
Depression is a debilitating common mental disorder more frequently observed among individuals exposed to traumatic events. Genetic factors explain approximately one third of the risk for depression, and multiple genetic loci have been identified. The UK Biobank concurrently assessed depression and reports of trauma exposure in 157,366 individuals with pre-existing genome-wide association study (GWAS) data. Using this dataset, we compared SNP-heritability, genetic correlations and polygenic risk scores across cases and controls, stratified by reported trauma exposure. Analyses used unrelated European ancestry individuals with high-quality genotype data (final N range: 24,094-98,720). Genetic correlations with depression were substantial between participants reporting trauma exposure and in unexposed individuals. However, estimates of heritability from common variants were greater in those reporting trauma exposure than in unexposed cases . Genetic correlations between depression and psychiatric traits were strong regardless of reported trauma exposure, whereas body mass index (and related phenotypes) was genetically correlated with depression status in trauma exposed (rather than unexposed) individuals. As such, in those reporting trauma exposure, the common genetic component of depression also reflects phenotypic correlates of depression such as body mass index. Our findings suggest that the environment acts on genetic risk for depression to increase the SNP-heritability of depression. Further, the homogeneity of genetic correlations in trauma unexposed depression (with psychiatric traits) and lack of correlation with BMI echoes earlier ideas of endogenous depression.