Causal associations between estradiol and mouth ulcers: A Mendelian randomization study

Abstract

People have difficulty in eating and speaking when they are suffering from mouth ulcers. Some studies suggest that estradiol is associated with the development and treatment of mouth ulcers, while some do not. To clarify the effect of estradiol on mouth ulcers, we performed 2-sample Mendelian randomization and multivariable Mendelian randomization (MVMR) analysis to evaluate their relationship. Data were obtained from the IEU OpenGWAS project and UK biobank, including male estradiol dataset (case/controls = 13,367/134,323), female estradiol dataset (case/controls = 37,461/126,524), mouth ulcers dataset (case/controls = 47,102/414,011). The causal associations were estimated by MR-Egger, weighted median, inverse-variance weighted (IVW) method, simple mode, and weighted mode. Cochran Q test, MR-Egger intercept test, MR-PRESSO tests, and leave-one-out analysis were used to examine sensitivity analyses. The MVMR controlling for depression, anxiety or panic attacks, severe stress and adjustment disorders was used to assess the effect of estradiol on mouth ulcers. Through screening, 13 single nucleotide polymorphisms (SNPs) of males and 2 SNPs of females in estradiol were used for harmonizing and MR analysis. The 2-sample MR analysis showed no causal association between estradiol of males and mouth ulcers (IVW, OR: 0.998, 95% confidence interval [95% CI]: 0.995–1.001, P = .18). Similar results were obtained between estradiol of females and mouth ulcers (IVW, OR: 1.000, 95% CI: 0.988–1.012, P = .97). No pleiotropy and heterogeneity were found and the results were robust (P > .05). After adjusting for the potential effects of confounders, estradiol of males and mouth ulcers still showed no causal association through MVMR analysis (P = .081). While MVMR analysis showed that the causal relationship between estradiol and mouth ulcers in women could not be statistical for the small number of SNPs. There was no evidence of a causal relationship between estradiol and mouth ulcers. The strategy of treating mouth ulcers with estradiol still needs to be confirmed by more studies.