Genetic susceptibility to severe COVID-19 and COVID-19 hospitalization and the risk of pre-eclampsia: A Mendelian randomization study

The association between COVID-19 and pre-eclampsia (PE) has been explored in epidemiological observational studies. However, due to methodological constraints, consensus has yet to be established. To address these limitations and investigate the potential causal relationship between COVID-19 and PE risk, we conducted a two-sample mendelian randomization (MR) analysis. MR analyses were performed to explore the genetic links and potential causality between PE and two COVID-19 phenotypes: hospitalization and severe disease, using available genome-wide association studies summary statistics. To strengthen causal inference, the primary inverse variance weighting (IVW) approach was complemented by four additional methods—MR-Egger, weighted median, weighted mode, and simple mode—offering a robust and comprehensive evaluation. The MR analysis from the IVW model showed genetic liabilities to COVID-19 hospitalization (odds ratio [OR]: 1.15, 95% confidence interval [CI]: 1.01 – 1.30) and severe COVID-19 (OR: 1.09, 95% CI: 1.01 – 1.18) to be associated with an increased PE risk. This MR analysis provides genetic evidence supporting a positive causal link between severe COVID-19 and the risk of PE.