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。