Investigation of the Causal Relationship Between Autoimmune Diseases and Premature Ovarian Insufficiency.

Background: POI is a multifactorial disease due to lack of estrogen resulting in symptoms such as insomnia, osteoporosis, and voiding disorders. For most women, fertility is affected. Autoimmune diseases are chronic diseases caused by disorders of immune regulation that often harm the ovaries. 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). 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. Our original data has been uploaded to Figshare, number and distribution of the DOI (DOI: 10.6084 / m9 Figshare. 25,525,585). Figshare is an open-access data storage and sharing platform designed to make it easy for researchers to store, manage, and share their research data, code, and other academic achievements. 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. We used MR methods to look into the causal association between 13 different kinds of AIDs and POI. Our study took a novel approach to traditional observational studies by adhering to the MR principle, which states that gamete formation depends on random assortment independent of external variables and that genetic variations precede outcomes, reducing the risk of reverse causality. The study found a correlation between SLE, MG, CD, and POI. Patients with SLE should have their ovarian function checked regularly, while those with POI should be aware of the possibility of CD and pay attention to their CD screening. MG, as a protective factor, can reduce the risk of POI.