Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank
Abstract
Depression is more frequent among individuals exposed to traumatic events. However, the relationship between trauma exposure and depression, including the role of genetic risk factors, is complex and poorly understood. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We compared MDD cases and healthy individuals reporting trauma exposure with those who did not (final sample size range: 24,094-92,957). The SNP-heritability of MDD was greater in participants reporting trauma exposure than in individuals not reporting trauma exposure. Genetic correlations between MDD and psychiatric traits were strong regardless of reported trauma exposure, whereas genetic correlations between MDD and both BMI (and related traits) and educational attainment were observed only in individuals reporting trauma exposure. The differing SNP-heritability and genetic correlations with MDD when stratified by reported trauma exposure suggests the genetic contribution to MDD is greater when additional risk factors are present.
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