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

Area of Science:

• Genetics
• Endocrinology
• Oral Medicine

Background:

• Mouth ulcers cause significant discomfort, affecting eating and speaking.
• The role of estradiol in the development and treatment of mouth ulcers is debated, with conflicting study results.
• Clarifying the relationship between estradiol and mouth ulcers is crucial for potential therapeutic strategies.

Purpose of the Study:

• To investigate the potential causal relationship between estradiol and mouth ulcers using Mendelian randomization.
• To evaluate the effect of male and female estradiol levels on the incidence of mouth ulcers.
• To assess the robustness of the association by controlling for potential confounding factors.

Main Methods:

• Utilized 2-sample Mendelian randomization (MR) and multivariable Mendelian randomization (MVMR) analyses.
• Employed large-scale genetic data from the IEU OpenGWAS project and UK Biobank for estradiol and mouth ulcer datasets.
• Employed various MR methods (MR-Egger, weighted median, IVW) and sensitivity analyses (Cochran Q, MR-Egger intercept, MR-PRESSO, leave-one-out).

Main Results:

• No statistically significant causal association was found between male estradiol levels and mouth ulcers (IVW P=0.18).
• No statistically significant causal association was found between female estradiol levels and mouth ulcers (IVW P=0.97).
• MVMR analysis confirmed no causal link between male estradiol and mouth ulcers, while the female association was inconclusive due to limited SNPs.

Conclusions:

• Current evidence does not support a causal relationship between estradiol and mouth ulcers in either sex.
• The potential therapeutic use of estradiol for mouth ulcers requires further investigation and validation in more extensive studies.
• Mendelian randomization analyses indicate that estradiol is unlikely to be a direct causal factor for mouth ulcers.