Response to Cai et al .’s letter on “Shared genetic associations and etiology between obstructive sleep apnea and cardiovascular diseases: a genome-wide cross-trait analysis and bidirectional Mendelian randomization analysis”

We sincerely thank Cai et al.1 for their interest in our recent study entitled ‘Shared genetic associations and etiology between obstructive sleep apnea and cardiovascular diseases: a genome-wide cross-trait analysis and bidirectional Mendelian randomization analysis’.2 Our study found strong genetic correlations between obstructive sleep apnoea (OSA) and various cardiovascular diseases (CVDs). Specifically, we identified OSA’s causal relation to heart failure as well as a reverse causal effect of atrial fibrillation on OSA, both of which were confirmed by Mendelian randomization (MR) analysis and latent causal variable analyses. At the same time, the study concludes a list of SNPs that are significantly connected to both OSA and CVDs, providing a genetic foundation for further research in this domain. Cai et al.1 raised a critical question under debate that deserves more discussion: if OSA truly exerts a biologically causal effect on cardiovascular outcomes, why have large randomized controlled trials failed to show that treating OSA with continuous positive airway pressure (CPAP) reduces cardiovascular events?