Genetic assessment of the causal relationship between obstructive sleep apnea and pulmonary hypertension: Mendelian...

Clinical observational studies have suggested a complex association between obstructive sleep apnea (OSA) and pulmonary hypertension (PH), but the causal relationship remains unclear due to the influence of confounding factors. In this study, a bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate whether the association between OSA and PH is causal.

We conducted a two-sample bidirectional Mendelian randomization (MR) study using pooled data from multiple European population-based genome-wide association studies (GWAS) on obstructive sleep apnea (OSA) and pulmonary hypertension (PH), including data from the GWAS catalog and the Finngen study. Statistical methods, including inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were employed to perform the Mendelian randomization (MR) analysis multiple times, with IVW being the primary method. A further meta-analysis of the MR results was conducted to assess the comprehensive causal effects across multiple MR outcomes. In the sensitivity analysis, MR-Egger, MR-PRESSO, and leave-one-out methods were employed to detect pleiotropy and heterogeneity.

The meta-analysis revealed a significant positive causal relationship between obstructive sleep apnea (OSA) and pulmonary hypertension (PH) (OR = 1.20, 95% CI [1.01-1.43], P = 0.04), while no significant negative causal relationship was observed (OR = 1.00, 95% CI [1.00-1.00], P = 0.99).

The MR-meta analysis indicated that genetically predicted obstructive sleep apnea (OSA) was significantly positively correlated with pulmonary hypertension (PH), and the underlying mechanism warrants further investigation.