Plasma polyunsaturated fatty acid concentrations and sleep apnea risk: A two-sample Mendelian randomization study

BACKGROUND: Previous observational studies have found that lower levels of circulating polyunsaturated fatty acids (PUFAs) were associated with a higher risk of sleep apnea (SA). However, the causality of the association remains unclear. MATERIALS AND METHODS: We used the two-sample Mendelian randomization (MR) study to assess the causal association of omega-3 and omega-6 fatty acids with SA. Single-nucleotide polymorphisms (SNPs) predicting the plasma level of PUFAs at the suggestive genome-wide significance level (p < 5 × 10(–6)) were selected as instrumental variables (IVs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) (n = ∼8,000) Consortium. For outcomes, the summary-level statistics of SA were obtained from the latest genome-wide association study (GWAS), which combined five cohorts with a total number of 25,008 SA cases and 172,050 snoring cases (total = 523,366). RESULTS: We found no association of α-linolenic acid (ALA) [odds ratio (OR) = 1.09 per% changed, 95% confidence interval (CI) 0.67–1.78], eicosapentaenoic acid (EPA) (OR = 0.94, 95% CI 0.88–1.01), docosapentaenoic acid (DPA) (OR = 0.95, 95% CI 0.88–1.02), and docosahexaenoic acid (DHA) (OR = 0.99, 95% CI 0.96–1.02) with the risk of SA using inverse-variance weighted (IVW) method. Moreover, for omega-6 PUFAs, no association between linoleic acid (LA) (OR = 0.98, 95% CI 0.96–1.01), arachidonic acid (AA) (1.00, 95% CI 0.99–1.01), and adrenic acid (AdrA) (0.93, 95% CI 0.71–1.21) with the risk of SA was found. Similarly, no associations of PUFAs with SA were found in single-locus MR analysis. CONCLUSION: In the current study, we first found that there is no genetic evidence to support the causal role of omega-3 and omega-6 PUFAs in the risk of SA. From a public health perspective, our findings refute the notion that consumption of foods rich in PUFAs or the use of PUFAs supplementation can reduce the risk of SA.