{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:50:46Z","timestamp":1791618646951,"version":"4.3.4"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Observational studies suggest the risk of primary ovarian insufficiency (POI) is increased in autoimmune disorders (AIDs), but it is unclear whether there is a causal relationship. Therefore, we aimed to investigate the bidirectional causality between 20 AIDs and POI using Mendelian randomization (MR) analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A bidirectional two-sample MR investigation was designed by using publicly accessible summary-level data from genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was performed as the main analysis, supplemented by several sensitivity analyses. Cochran Q test was used to evaluate SNP estimate heterogeneity. MR-Egger and MR-PRESSO methods were utilized to detect horizontal pleiotropy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The MR analyses revealed that genetically determined coeliac disease (CeD) (OR = 1.124, 95% CI 1.033-1.224, P = 0.007), vitiligo (OR = 1.092, 95% CI 1.003-1.188; P = 0.042), systemic lupus erythematosus (SLE) (OR = 1.122, 95% CI 1.030-1.223, P = 0.008), and selective immunoglobulin A deficiency (SIgAD) (OR = 0.866, 95% CI: 0.776-0.967, P = 0.011) exhibited significant causal relationships with POI. We also found suggestive evidence of positive effect of Addison\u2019s disease (AD) towards POI (OR<jats:sub>5e-6<\/jats:sub> = 1.076, 95% CI 1.002-1.154, P = 0.043).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This comprehensive MR analysis indicated that SLE, CeD, vitiligo, and AD caused an increased risk of POI, SIgAD was associated with a decreased risk of POI. These insights carry profound clinical implications, particularly emphasizing the early intervention for women with AIDs\/POI who wish to preserve their reproductive potential or plan for future pregnancies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1417896","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T04:26:16Z","timestamp":1733718376000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Primary ovarian insufficiency consequence of autoimmune diseases: a bidirectional two-sample Mendelian randomization 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