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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Reproduction
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1417896

Primary ovarian insufficiency consequence of autoimmune diseases: a bidirectional two-sample mendelian randomization study

Provisionally accepted
Yongming Du Yongming Du *Yichao Hu Yichao Hu *Yuehua Sheng Yuehua Sheng Tianhong Zhu Tianhong Zhu Shenping Liu Shenping Liu *Huiqing Ding Huiqing Ding *Yutao Guan Yutao Guan *
  • Ningbo First Hospital, Ningbo, China

The final, formatted version of the article will be published soon.

    Background: 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.Methods: 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.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's disease (AD) towards POI (OR5e-6 = 1.076, 95% CI 1.002-1.154, P = 0.043).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.

    Keywords: autoimmune disease, Primary Ovarian Insufficiency, Mendelian randomization, single-nucleotide polymorphisms, causal association

    Received: 15 Apr 2024; Accepted: 20 Nov 2024.

    Copyright: © 2024 Du, Hu, Sheng, Zhu, Liu, Ding and Guan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yongming Du, Ningbo First Hospital, Ningbo, China
    Yichao Hu, Ningbo First Hospital, Ningbo, China
    Shenping Liu, Ningbo First Hospital, Ningbo, China
    Huiqing Ding, Ningbo First Hospital, Ningbo, China
    Yutao Guan, Ningbo First Hospital, Ningbo, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.