Genetic association between coffee/caffeine consumption and the risk of obstructive sleep apnea in the European population: a two-sample Mendelian randomization study.

BACKGROUND: The association between coffee/caffeine consumption and obstructive sleep apnea (OSA) risk remains unclear. PURPOSE: To determine the relationship between coffee/caffeine consumption and the risk of OSA, using the Mendelian randomization (MR) method in the European population. METHODS: Two sets of coffee consumption-associated genetic variants were, respectively, extracted from the recent genome-wide meta-analysis (GWMA) and genome-wide association study (GWAS) of coffee consumption. Taking other caffeine sources into account, genetic variants associated with caffeine consumption from tea and plasma caffeine (reflecting total caffeine intake) were also obtained. The inverse variance weighted (IVW) technique was utilized as the primary analysis, supplemented by the MR-Egger, weighted-median, and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) techniques. Leave-one-out (LOO) analysis was performed to assess whether the overall casual estimates were driven by a single SNP. Additional sensitivity analyses were performed using similar methods, while the genetic variants associated with confounders, e.g., body mass index and hypertension, were excluded. RESULTS: The IVW method demonstrated that coffee consumption GWMA (OR: 1.065, 95% CI 0.927-1.224, p = 0.376), coffee consumption GWAS (OR: 1.665, 95% CI 0.932-2.977, p = 0.086), caffeine from tea (OR: 1.198, 95% CI 0.936-1.534, p = 0.151), and blood caffeine levels (OR: 1.054, 95% CI 0.902-1.231, p = 0.508) were unlikely to be associated with the risk of OSA. The other three methods presented similar results, where no significant associations were found. No single genetic variant was driving the overall estimates by the LOO analysis. These findings were also supported by the sensitivity analyses with no confounding genetic variants. CONCLUSION: Our study found no association between coffee/caffeine consumption and the risk of OSA.