Mendelian randomization analysis: causal link between hyperthyroidism/thyrotoxicosis and ovarian cancer

The purpose of this study was to use a two-sample Mendelian randomization (MR) approach to explore the causal link between hyperthyroidism/thyrotoxicosis and ovarian cancer (OC).

By leveraging genome-wide association study (GWAS) data from publicly available databases, we identified single nucleotide polymorphisms (SNPs) representing genetic variants for both hyperthyroidism/thyrotoxicosis and OC. We employed the inverse variance weighted method (IVW) to assess the association between hyperthyroidism/thyrotoxicosis and the risk of OC. Further, we evaluated SNP heterogeneity using the Cochran's Q test and detected the presence of outlier SNPs using the MR-PRESSO test. To examine the pleiotropy of SNPs, we employed the MR-Egger intercept test. Additionally, a "leave-one-out" sensitivity analysis was conducted to assess the influence of individual SNPs on the MR results. Finally, we performed a reverse MR analysis to explore the possibility of reverse causality.

The results of the IVW analysis indicated a causal relationship between hyperthyroidism/thyrotoxicosis and OC, with hyperthyroidism/thyrotoxicosis increasing the incidence of OC (p < 0.05). According to the MR-Egger intercept and MR-PRESSO global tests, no horizontal pleiotropy was observed in this study (P > 0.05). Sensitivity analysis using "leave-one-out" method indicated the stability of these genetic variants.

Our systematic analyses provide evidence supporting a potential causal relationship between hyperthyroidism/thyrotoxicosis and the risk of OC.