Wang Jiao, Huang Yingyue, Yang Huiling, Lin Zihong, Campos Adrian I, Rentería Miguel E, Xu Lin
School of Public Health, Sun Yat-sen University, Guangzhou, China.
Eastern-Fusion Master Studio of Hezhou, Hezhou, China.
Front Nutr. 2022 Aug 18;9:956900. doi: 10.3389/fnut.2022.956900. eCollection 2022.
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.
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 ( < 5 × 10) were selected as instrumental variables (IVs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) ( = ∼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).
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.
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.
既往观察性研究发现，循环多不饱和脂肪酸（PUFA）水平较低与睡眠呼吸暂停（SA）风险较高相关。然而，这种关联的因果关系仍不明确。
我们采用两样本孟德尔随机化（MR）研究来评估ω-3和ω-6脂肪酸与SA之间的因果关联。从基因组流行病学心脏与衰老研究队列（CHARGE）（n = ∼8,000）联盟中，选择在全基因组显著水平（< 5×10）提示血浆PUFA水平的单核苷酸多态性（SNP）作为工具变量（IV）。对于结局，SA的汇总统计数据来自最新的全基因组关联研究（GWAS），该研究合并了5个队列，共有25,008例SA病例和172,050例打鼾病例（总计 = 523,366）。
我们使用逆方差加权（IVW）方法发现，α-亚麻酸（ALA）[比值比（OR）=每变化1%为1.09，95%置信区间（CI）0.67 - 1.78]、二十碳五烯酸（EPA）（OR = 0.94，95% CI 0.88 - 1.01）、二十二碳五烯酸（DPA）（OR = 0.95，95% CI 0.88 - 1.02）和二十二碳六烯酸（DHA）（OR = 0.99，95% CI 0.96 - 1.02）与SA风险无关联。此外，对于ω-6多不饱和脂肪酸，亚油酸（LA）（OR = 0.98，95% CI 0.96 - 1.01）、花生四烯酸（AA）（1.00，95% CI 0.99 - 1.01）和肾上腺酸（AdrA）（0.93，95% CI 0.71 - 1.21）与SA风险也无关联。同样，在单基因座MR分析中未发现PUFA与SA有关联。
在本研究中，我们首次发现没有遗传证据支持ω-3和ω-6多不饱和脂肪酸在SA风险中的因果作用。从公共卫生角度来看，我们的研究结果反驳了食用富含PUFA的食物或使用PUFA补充剂可降低SA风险的观点。
