<b>Investigation of the causal relationship between autoimmune diseases and premature ovarian insufficiency</b>

<b>Background</b>Recent epidemiological studies have reported a correlation between autoimmune diseases (AIDs) and premature ovarian insufficiency (POI). This study aims to explore the causal relationship between AIDs and POI using bidirectional two-sample Mendelian randomization (MR).<b>Method</b>The data regarded AIDs from the Genome-wide association studies (GWAS) Catalog and the IEU Open GWAS project. POI was obtained from the FinnGen Study. All data were extracted from European populations. We used bidirectional MR with inverse variance weighting (IVW) as the primary study method, supplemented by weighted median and MR Egger validation analyses.<b>Result</b>Our study showed that the liability to Systemic lupus erythematosus (SLE) and Myasthenia gravis (MG) affect POI risk. The reverse MR analysis supported the effect of POI on Crohn's disease (CD). The result of the IVW method was supported by the sensitivity MR analysis. The IVW results showed that the odds ratio (OR) value of SLE was 1.13 and MG was 0.83. In the reverse MR, the OR value of CD was 1.22.<b>Conclusion</b>In summary, our MR study supports a causal relationship between SLE, MG, CD, and POI risk in the European population. We significantly reduce the impact of confounding factors and reverse causation. It provides an innovative methodology for investigating the biological mechanism, early diagnosis, individualized treatment, and prevention.

<b>研究背景</b>近期流行病学研究表明，自身免疫性疾病（autoimmune diseases, AIDs）与早发性卵巢功能不全（premature ovarian insufficiency, POI）之间存在相关性。本研究拟采用双向两样本孟德尔随机化（bidirectional two-sample Mendelian randomization, MR）方法，探究自身免疫性疾病与早发性卵巢功能不全之间的因果关联。<b>研究方法</b>本研究纳入的自身免疫性疾病数据来源于全基因组关联研究（Genome-wide association studies, GWAS）数据库及IEU开放全基因组关联研究项目；早发性卵巢功能不全数据来源于FinnGen研究。所有研究数据均来自欧洲人群。本研究以逆方差加权（inverse variance weighting, IVW）法作为双向孟德尔随机化分析的主要方法，并辅以加权中位数法与MR Egger法进行验证分析。<b>研究结果</b>本研究结果显示，系统性红斑狼疮（Systemic lupus erythematosus, SLE）与重症肌无力（Myasthenia gravis, MG）的易感性可影响早发性卵巢功能不全的发病风险。反向孟德尔随机化分析证实，早发性卵巢功能不全可对克罗恩病（Crohn's disease, CD）的发生产生影响。逆方差加权法的分析结果得到了敏感性孟德尔随机化分析的验证。逆方差加权法结果显示，系统性红斑狼疮的比值比（odds ratio, OR）为1.13，重症肌无力的比值比为0.83；反向孟德尔随机化分析中，克罗恩病的比值比为1.22。<b>研究结论</b>综上，本孟德尔随机化研究证实，欧洲人群中系统性红斑狼疮、重症肌无力、克罗恩病与早发性卵巢功能不全的发病风险存在因果关联。本研究有效降低了混杂因素与反向因果关联的影响，为探索相关疾病的生物学机制、早期诊断、个体化治疗及疾病预防提供了创新的研究方法。

搜集汇总

背景与挑战

背景概述

该数据集基于欧洲人群的GWAS数据，使用双向双样本孟德尔随机化方法，研究自身免疫性疾病与早发性卵巢功能不全的因果关系。结果显示系统性红斑狼疮和重症肌无力影响POI风险，而POI影响克罗恩病风险，为疾病机制和预防提供了方法学支持。