Abstract：
OBJECTIVE: The simultaneous occurrence of primary ovarian insufficiency (POI) and autoimmune diseases has been noted and debated in some epidemiological research. This bidirectional two-sample Mendelian randomization (MR) study aimed to investigate the causal relationships between autoimmune diseases and POI.
METHODS: We obtained summary-level data for ten autoimmune diseases and POI from published large-scale genome-wide association studies and the FinnGen consortium of European ancestry. A series of filtering steps was performed to discern independent genetic variants. Causal estimates were mainly calculated by the inverse variance weighting method and verified through multiple sensitivity analyses.
RESULTS: Of the ten autoimmune diseases, genetically predicted Addison\'s disease (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.09-1.47, P = 0.003) and systemic lupus erythematosus (OR = 1.12, 95% CI 1.02-1.24, P = 0.021) were associated with an increased risk of POI, and sensitivity analyses confirmed the robustness of the results. In addition, there were weak associations between liability to POI and elevated risks of type 1 diabetes (OR = 1.05, 95% CI 1.00-1.10, P = 0.046) and autoimmune thyroid disease (OR = 1.03, 95% CI 1.01-1.05, P = 0.015).
CONCLUSIONS: This study revealed that Addison\'s disease and systemic lupus erythematosus are potential risk factors for POI, underscoring the necessity to consider the impact of autoimmune factors in the diagnosis and treatment of POI.
METHODS: We obtained summary-level data for ten autoimmune diseases and POI from published large-scale genome-wide association studies and the FinnGen consortium of European ancestry. A series of filtering steps was performed to discern independent genetic variants. Causal estimates were mainly calculated by the inverse variance weighting method and verified through multiple sensitivity analyses.
RESULTS: Of the ten autoimmune diseases, genetically predicted Addison\'s disease (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.09-1.47, P = 0.003) and systemic lupus erythematosus (OR = 1.12, 95% CI 1.02-1.24, P = 0.021) were associated with an increased risk of POI, and sensitivity analyses confirmed the robustness of the results. In addition, there were weak associations between liability to POI and elevated risks of type 1 diabetes (OR = 1.05, 95% CI 1.00-1.10, P = 0.046) and autoimmune thyroid disease (OR = 1.03, 95% CI 1.01-1.05, P = 0.015).
CONCLUSIONS: This study revealed that Addison\'s disease and systemic lupus erythematosus are potential risk factors for POI, underscoring the necessity to consider the impact of autoimmune factors in the diagnosis and treatment of POI.
摘要：
目的：原发性卵巢功能不全（POI）和自身免疫性疾病的同时发生在一些流行病学研究中已经被注意到并存在争议。这项双向双样本孟德尔随机化（MR）研究旨在研究自身免疫性疾病与POI之间的因果关系。
方法：我们从已发表的大规模全基因组关联研究和FinnGen欧洲血统联盟获得了十种自身免疫性疾病和POI的汇总水平数据。进行一系列过滤步骤以辨别独立的遗传变体。因果估计主要通过方差逆加权方法计算，并通过多重敏感性分析进行验证。
结果：在十种自身免疫性疾病中，遗传预测的Addison病（比值比[OR]=1.26，95％置信区间[CI]：1.09-1.47，P=0.003）和系统性红斑狼疮（OR=1.12，95％CI1.02-1.24，P=0.021）与POI风险增加相关，敏感性分析证实了结果的稳健性。此外,POI倾向与1型糖尿病风险升高(OR=1.05,95%CI1.00-1.10,P=0.046)和自身免疫性甲状腺疾病(OR=1.03,95%CI1.01-1.05,P=0.015)之间的相关性较弱.
结论：这项研究表明，艾迪生病和系统性红斑狼疮是POI的潜在危险因素，强调在POI的诊断和治疗中必须考虑自身免疫因素的影响。
方法：我们从已发表的大规模全基因组关联研究和FinnGen欧洲血统联盟获得了十种自身免疫性疾病和POI的汇总水平数据。进行一系列过滤步骤以辨别独立的遗传变体。因果估计主要通过方差逆加权方法计算，并通过多重敏感性分析进行验证。
结果：在十种自身免疫性疾病中，遗传预测的Addison病（比值比[OR]=1.26，95％置信区间[CI]：1.09-1.47，P=0.003）和系统性红斑狼疮（OR=1.12，95％CI1.02-1.24，P=0.021）与POI风险增加相关，敏感性分析证实了结果的稳健性。此外,POI倾向与1型糖尿病风险升高(OR=1.05,95%CI1.00-1.10,P=0.046)和自身免疫性甲状腺疾病(OR=1.03,95%CI1.01-1.05,P=0.015)之间的相关性较弱.
结论：这项研究表明，艾迪生病和系统性红斑狼疮是POI的潜在危险因素，强调在POI的诊断和治疗中必须考虑自身免疫因素的影响。
