Investigation of the causal relationship between autoimmune diseases and premature ovarian insufficiency

BackgroundRecent 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).MethodThe 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.ResultOur 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.ConclusionIn 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.