Genome-wide gene-environment analyses of depression and reported lifetime traumatic experiences in UK Biobank

Depression is more frequently observed among individuals exposed to traumatic events. The relationship between trauma exposure and depression, including the role of genetic variation, is complex and poorly understood. The UK Biobank concurrently assessed depression and reported trauma exposure in 126,522 genotyped individuals of European ancestry. We compared the shared aetiology of depression and a range of phenotypes, contrasting individuals reporting trauma exposure with those who did not (final sample size range: 24,094-92,957). Depression was heritable in participants reporting trauma exposure and in unexposed individuals, and the genetic correlation between the groups was substantial and not significantly different from 1. Genetic correlations between depression and psychiatric traits were strong regardless of reported trauma exposure, whereas genetic correlations between depression and body mass index (and related phenotypes) were observed only in trauma exposed individuals. The narrower range of genetic correlations in trauma unexposed depression and the lack of correlation with BMI echoes earlier ideas of endogenous depression.