Causal associations of sleep apnea, snoring with cardiovascular diseases, and the role of body mass index: a two-sample Mendelian randomization study

Aims Previously, observational studies have identified associations between sleep apnea (SA) and cardiovascular diseases (CVDs), whereas whether the associations are causal remain unclear. Methods and results We used the bi-directional, two-sample Mendelian randomization (MR) study to assess the existence and direction of the causal relationship between SA or snoring and CVDs. Multivariable MR (MVMR) was used to assess the direct effect of SA on CVDs after adjusting for body mass index (BMI). Single-nucleotide polymorphisms (SNPs) associated with SA and snoring were obtained from the latest genome-wide association study, which combined five cohorts with a total number of 25 008 SA cases and 172 050 snoring cases (total = 523 366). Among the analytic sample of 523 366 individuals (25 008 SA cases and 172 050 snoring cases), and after correcting for multiple testing, inverse-variance weighted (IVW) showed that SA and snoring increased the risk of hypertension [odds ratio (OR) = 1.03, 95% CI 1.02-1.05 and 1.05, 1.03-1.07], and coronary artery disease (CAD) (1.41,1.19-1.67 and 1.61,1.26-2.07) with all false-discovery rate (FDR) < 0.05, but such associations were decreased dramatically after adjusting for BMI using MVMR-IVW (0.06 < FDRBMI adjusted < 0.20). SA and snoring were not associated with atrial fibrillation (AF), heart failure (HF), or stroke. The presence of hypertension may increase the risk of SA (1.53, 1.04-2.25), but this association did not pass multiple comparisons (FDR > 0.05). Discussion Our results suggest that SA and snoring increased the risk of hypertension and CAD, and these associations may partly be driven by BMI. Conversely, no evidence of CVDs causally influencing SA or snoring was found. Lay Summary This two-sample Mendelian randomization analysis shows that sleep apnea (SA) and snoring increased the risk of hypertension and coronary artery diseases, and these associations may partly be driven by the body mass index.Further studies clarifying the role of adiposity in the effect of SA and snoring on cardiovascular diseases (CVDs) are needed.No evidence of CVDs causally influencing SA or snoring was found.