Causal effects of endometriosis on SLE, RA and SS risk: evidence from meta-analysis and Mendelian randomization

Abstract

Background Endometriosis is an underdiagnosed disorder that affects an estimated 6-10% of women of reproductive age. Endometriosis has been reported in epidemiological studies to be associated with autoimmune diseases. However, the relationship remains controversial. Methods A meta-analysis of observational studies was undertaken to evaluate the risk of autoimmune diseases in patients with endometriosis. The relevant studies were retrieved via the databases Medline, Embase and Web of Science until July 20, 2023. Mendelian randomization (MR) was subsequently utilized to scrutinize the causal influence of genetic predisposition toward endometriosis on three autoimmune diseases. Results The meta-analysis findings revealed a relationship between endometriosis and the onset of SLE (cohort studies: RR = 1.77, 95% confidence interval (CI): 1.47–2.13, I 2 = 0%; Case-control and cross-sectional studies: OR = 5.23, 95% CI: 0.74–36.98, I 2 = 98%), RA (cohort studies: RR = 2.18, 95% CI: 1.85–2.55, I 2 = 92%; Case-control and cross-sectional studies: OR = 1.40, 95% CI: 1.19–1.64, I 2 = 0%) and SS (cohort studies: RR = 1.49, 95% CI: 1.34–1.66, I 2 = 0%). Similarly, in our MR study, the results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for SLE (OR = 1.915, 95% CI: 1.204–3.045, p = 0.006) and RA (OR = 1.005, 95% CI: 1.001–1.009, p = 0.014). Conclusions Both our meta-analysis and MR study indicate that endometriosis increases the risk of autoimmune diseases. These findings not only broaden our understanding of the genetic mechanisms underlying the comorbidity of endometriosis and autoimmune diseases, but also offer a new strategy for autoimmune disease prevention.