Observational and Genetic Analyses of Traumatic Experiences and Endometriosis

Abstract

Importance: Although psychological traumas have been associated with endometriosis, limited information is available regarding the role of trauma type and genetic predisposition.

Objective: To examine the relationship between traumatic experiences and endometriosis using observational and genetically informed analyses.

Design, setting, and participants: For this case-control study, the analyses were performed between May 13, 2023, and September 30, 2024. Genotypic and phenotypic information was combined from UK Biobank individual-level data (up to 8276 patients with endometriosis and 240 117 female controls) with genome-wide information available from a large meta-analysis (European ancestry: 21 779 patients and 449 087 female controls; East Asian ancestry: 1713 patients and 1581 female controls) and the FinnGen cohort (16 588 patients and 111 583 female controls of European descent).

Main outcomes and measures: Phenotypic associations via multiple regression; latent-class analysis (LCA) to investigate the co-occurrence patterns of different traumatic experiences in endometriosis cases and controls; genetic correlation and polygenic risk scoring (PRS) analyses to assess pleiotropy linking traumatic events to endometriosis.

Results: Up to 8276 women with endometriosis (mean [SD] age, 53.2 [13.0] years) and 240 117 female controls (mean [SD] age, 56.5 [9.6] years) were investigated in the study. Women with endometriosis were more likely to report childhood and adulthood traumatic experiences and stressful events (eg, contact trauma odds ratio [OR], 1.28; 95% CI, 1.02-1.26). Our LCA highlighted the association of endometriosis with emotional and physical trauma (225 [8%] vs 3948 [5%]; P < 2.2 × 10-16) and sexual trauma (414 [5%] vs 3158 [4%]; P = 2.9 × 10-3). Unaffected women (controls) were more likely assigned to the "no trauma" latent class (563 [20%] vs 18 949 [24%]; P = 7.4 × 10-14). Our genetic correlation (rg) analyses linked endometriosis to multiple trauma-related outcomes, including posttraumatic stress disorder (meta-analysis rg = 0.31, P = 7.1 × 10-16; FinnGen rg = 0.26, P = 4.7 × 10-15) and childhood maltreatment (meta-analysis rg = 0.23, P = 1.3 × 10-6; FinnGen rg = 0.16, P = 1 × 10-4). Endometriosis PRS was associated with increased odds of the disease (β = 0.31, P < 2.2 × 10-16), but no interaction was observed with different types of trauma events.

Conclusions and relevance: The present study comprehensively investigated the impact of childhood and adulthood traumatic experiences and stressful events on endometriosis. In particular, our findings highlight the potential association between contact traumas and endometriosis, which appears to be independent of the disease genetic predisposition.