Endometriosis, Psychiatric Condition Associations Tied to Pleiotropic Mechanisms

This is the first large-scale study to provide genetic and phenotypic evidence of the processes underlying the psychiatric comorbidities of endometriosis.

Associations between women with endometriosis and comorbid psychiatric conditions can be linked to pleiotropic mechanisms, according to study results published in JAMA Network Open

Researchers conducted a genetic association study from September 13, 2021, to June 24, 2022, with 202,276 women participants. Among the participants, 8276 were diagnosed with endometriosis and 194,000 were control participants. The mean (SD) age of the participants with endometriosis was 53.1 (7.9) years and 56.7 (7.9) years for those without endometriosis. 

Individual genotype and phenotype data were collected from UK Biobank (UKB). Genome-wide association statistics were collected from the Psychiatric Genomics Consortium (PGC), the Million Veteran Program (MVP), the FinnGen study, and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.

A multivariate regression analysis was performed, and after accounting for several patient-related factors, the researchers found that endometriosis was associated with increased odds of depression (OR, 3.61; 95% CI, 3.32-3.92), eating disorders (OR, 2.24; 95% CO, 1.96-4.41), and anxiety (OR, 2.61; 95% CI, 2.30-2.97).  

These findings highlight that endometriosis is associated with women’s mental health through pleiotropic mechanisms.

Genetic correlation and single-nucleotide variant (SNV) heritability was measured with the Scalable Genetic Correlation Estimator method using the individual phenotypic and genotypic data gathered from UKB. The researchers found that the mean (SE) female-specific SNV-based heritability (SNV-h2) was 0.086 (0.015) for endometriosis, 0.019 (0.003) for depression, 0.012 (0.002) for anxiety, and 0.004 (0.002) for eating disorders. The associations described between correlation (rg) values. The rg value was 0.36 (P =1.5×10-9) for depression, 0.33 (P =1.5×10-5) for anxiety, and 0.61 (P =.03) for eating disorders. 

One-sample Mendelian randomization was conducted to measure the genetic associations between endometriosis, anxiety, depression, and eating disorders. Genetic liabilities to depression or anxiety were observed to be associated with endometriosis. The OR for depression was 1.09 (95% CI, 1.08-1.11) and 1.39 for anxiety (95% CI, 1.13-1.65). There was no significant genetic association found between eating disorders and endometriosis (OR, 0.73; 95% CI, 0.04-1.43). 

Finally, a genome-wide analysis (GWAS) of pleiotropic analyses was conducted to determine the pleiotropic loci associated with endometriosis, anxiety, depression, and eating disorders. The researchers identified DGKB rs12666606 as a locus demonstrating pleiotropy between endometriosis and depression. 

A major limitation of the study is the fact that those with a chronic mental illness may have a higher likelihood of endometriosis diagnosis rates as they are more likely to be in a clinical setting; this confounding variable could potentially alter the significance of the association between endometriosis and depression or anxiety. 

Researchers conclude, “These findings highlight that endometriosis is associated with women’s mental health through pleiotropic mechanisms.” 


Koller D, Pathak GA, Wendt FR, et al. Epidemiologic and genetic associations of endometriosis with depression, anxiety, and eating disorders. JAMA Netw Open. 2023;6(1):e2251214. doi:10.1001/jamanetworkopen.2022.51214