Epidemiologic and Genetic Associations of Endometriosis With Depression, Anxiety, and Eating Disorders

Key Points

Question

What biological mechanisms are associated with endometriosis with mental health comorbidities?

Findings

This genetic association study of 8276 women with endometriosis and 194 000 female controls found that pleiotropy is likely associated with the comorbid depression, anxiety, and eating disorders observed in patients with endometriosis.

Meaning

This study highlights the importance of considering endometriosis pathogenesis from a more comprehensive perspective, including both mental and physical health.

Abstract

This genetic association study uses phenotypic and genetic association analyses of unrelated women to test the comorbidity of endometriosis with depression, anxiety, and eating disorders.

Abstract

Importance

Endometriosis is a common chronic gynecologic pathology with a large negative impact on women’s health. Beyond severe physical symptoms, endometriosis is also associated with several psychiatric comorbidities, including depression and anxiety.

Objective

To investigate whether pleiotropy contributes to the association of endometriosis with depression, anxiety, and eating disorders.

Design, Setting, and Participants

This genetic association study was performed between September 13, 2021, and June 24, 2022, in 202 276 unrelated female participants. Genotypic and phenotypic information from the UK Biobank was combined with genome-wide association statistics available from the Psychiatric Genomics Consortium (11 countries), the Million Veteran Program (US), the FinnGen study (Finland), and the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium (5 countries).

Main Outcomes and Measures

The main outcomes were the phenotypic and genetic associations of endometriosis with anxiety, depression, and eating disorders.

Results

A total of 8276 women with endometriosis (mean [SD] age, 53.1 [7.9] years) and 194 000 female controls (mean [SD] age, 56.7 [7.9] years) were included in the study. In a multivariate regression analysis accounting for age, body mass index, socioeconomic status, chronic pain–related phenotypes, irritable bowel syndrome, and psychiatric comorbidities, endometriosis was associated with increased odds of depression (odds ratio [OR], 3.61; 95% CI, 3.32-3.92), eating disorders (OR, 2.94; 95% CI, 1.96-4.41), and anxiety (OR, 2.61; 95% CI, 2.30-2.97). These associations were supported by consistent genetic correlations (rg) (depression rg, 0.36, P = 1.5 × 10 ⁻⁹; anxiety rg, 0.33, P = 1.17 × 10 ⁻⁵; and eating disorders rg, 0.61, P = .02). With the application of a 1-sample mendelian randomization, the genetic liabilities to depression and anxiety were associated with increased odds of endometriosis (depression: OR, 1.09; 95% CI, 1.08-1.11; anxiety: OR, 1.39; 95% CI, 1.13-1.65). A genome-wide analysis of pleiotropic associations shared between endometriosis and psychiatric disorders identified 1 locus, DGKB rs12666606, with evidence of pleiotropy between endometriosis and depression after multiple testing correction ( z = −9.46 for endometriosis, z = 8.10 for depression, P = 5.56 × 10 ⁻⁸; false discovery rate q = 4.95 × 10 ⁻⁴).

Conclusions and Relevance

These findings highlight that endometriosis is associated with women’s mental health through pleiotropic mechanisms. To our knowledge, this is the first large-scale study to provide genetic and phenotypic evidence of the processes underlying the psychiatric comorbidities of endometriosis.