Bidirectional Mendelian randomization and cross-sectional study reveal depression as a causal risk factor for endometriosis

Endometriosis (EMs) and depression are both common conditions that have a significant negative impact on quality of life. However, it is still unclear about the relationship between them. The study was designed to investigate the phenotypic and causal association between depression and EMs. For its nationally representative sample, comprehensive health data and publicly accessibility, we chose data from the National Health and Nutrition Examination Survey for our observational study section including 1393 participants in 2005 to 2006 year cycle which contains information both on depression assessed by the Patient Health Questionnaire 9 and self-reported EMs. Initially, we conducted logistic regression analysis to evaluate phenotypic association between depression and EMs utilizing extensive data taken from National Health and Nutrition Examination Survey. Then, using data from the genome-wide association study (female self-reported depression data: N = 194,153 and female medical-recorded depression data: N = 192,680 from UK Biobank where sex-stratified data was provided; EMs data: N = 150,350 from FinnGen consortium database), we assessed the genetically predicted association performing bidirectional two-sample Mendelian randomization (MR) analysis. Inverse-variance weighted method was employed as the main MR analysis. The Weighted median, MR Egger, Simple mode, Weighted mode, and MR pleiotropy residual sum and outlier test were also performed to assess the robustness of our findings. EMs was present in almost 13.64% of the participants in the depression group, which was much greater than the 6.63% in the non-depression group. Depression and EMs were positively correlated in the observational analysis (OR = 2.44, 95%CI = 1.26-4.74). Furthermore, each greater Patient Health Questionnaire 9 score was associated with a 7% increased risk of EMs. EMs did not have a genetically informed influence on depression, while depression clearly had a genetically predicted effect on EMs, according to bidirectional MR analysis. This study shows a genetically predicted association between depression and EMs as well as a favorable phenotypic correlation. It implies that monitoring of diseases of the reproductive system, such as EMs, in female patients with mood disorders and treating them from a multidisciplinary perspective should not be neglected. Further large-scale prospective cohort studies or mechanistic research are warranted to confirm these results and explore the underlying biological mechanisms.