Causal relationships between obstructive sleep apnea and pre-eclampsia: A Mendelian randomization study

Introduction: Previous observational investigations have revealed a possible association between obstructive sleep apnea (OSA) and pre-eclampsia (PE), but they are limited by confounding factors. Objective: We employed genetic data in a two-sample Mendelian randomization (MR) study to investigate the causal link between PE and OSA. Methods: To assess the causal influences of OSA and PE, this MR investigation used single-nucleotide polymorphisms (SNPs) as instrumental variables. The FinnGen database provided the genetic information for OSA, which included 50,200 cases and 401,484 controls, whereas data for PE were sourced from a study with 1728 cases and 192,399 controls. Sensitivity analyses were performed to check for pleiotropy and heterogeneity, and reverse MR was carried out to analyze potential bidirectional relationships. Results: OSA and an elevated PE risk were found to be significantly correlated by the inverse variance weighted analysis (odds ratio [OR] [95% confidence interval (CI)] = 1.640 [1.166–2.306]; p=0.004). Sensitivity analyses revealed no heterogeneity or pleiotropy, as verified by MR-Egger intercept analysis and Cochran’s Q test. Leave-one-out analysis showed that no individual SNP drove the results. Evidence of a causal connection between PE and OSA was not found by reverse MR analysis (OR [95% CI] = 0.970 [0.927–1.015]; p=0.194). Conclusion: This MR investigation points to a genetically supported causal link between higher PE risk and OSA.