The Potential Role of Female Sex Hormones in Patients With Inflammatory Bowel Disease: A 2-Sample Mendelian Randomization Study

作者：J. Pan, Wenxi Jiang, Linying Xin, Jiali Wu, Shefeng Zhu, Zhaoxue Liu, Zhe Shen · 发表于：Clinical and Translational Gastroenterology · 年份：2024 · DOI：10.14309/ctg.0000000000000748 · 被引用次数：7 · 研究领域：Genetic Associations and Epidemiology、Inflammatory Bowel Disease、Pregnancy and Medication Impact

INTRODUCTION: An association between female sex hormones and inflammatory bowel disease (IBD) has been reported in epidemiological studies. However, a solid causal relationship has not been established. Therefore, we performed a 2-sample Mendelian randomization (MR) study to explore the causal association between genetically predicted female sex hormone exposure, especially estrogen, and IBD. METHODS: Genetic variants for female sex hormone exposure (ovulatory function, reproductive function, oral contraceptive pills, and hormone replacement therapy) were obtained from genome-wide association studies. Summary statistics for IBD were derived from the International Inflammatory Bowel Disease Genetics Consortium. We applied inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods in this MR study. Heterogeneity, horizontal pleiotropy, and sensitivity analyses were conducted to confirm the accuracy and robustness of our results. RESULTS: Our study found that genetically predicted age at menarche was associated with an increased risk of Crohn's disease (odds ratio [OR] IVW 1.235, 95% confidence interval [CI] 1.028-1.484, P = 0.024), genetically predicted age of the last used hormone replacement therapy was associated with an increased risk of ulcerative colitis (OR WM 1.636, 95% CI 1.011-2.648, P = 0.045), and genetically predicted number of live births was related to a decreased risk of Crohn's disease (OR IVW 0.583, 95% CI 0.373-0.912, P = 0.018). DISCUSSION: ...