Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
Department of Internal Medicine, Armed Forces Capital Hospital, Gyeonggi-do 13574, Korea.
Nutrients. 2021 Apr 28;13(5):1490. doi: 10.3390/nu13051490.
We aimed to investigate the causal effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on the risk of coronary artery disease (CAD) through Mendelian randomization (MR) analysis. This MR study utilized a genetic instrument developed from previous genome-wide association studies for various serum n-3 and n-6 PUFA levels. First, we calculated the allele scores for genetic predisposition of PUFAs in individuals of European ancestry in the UK Biobank data ( = 337,129). The allele score-based MR was obtained by regressing the allele scores to CAD risks. Second, summary-level MR was performed with the CARDIoGRAMplusC4D data for CAD ( = 184,305). Higher genetically predicted eicosapentaenoic acid and dihomo-gamma-linolenic acid levels were significantly associated with a lower risk of CAD both in the allele-score-based and summary-level MR analyses. Higher allele scores for linoleic acid level were significantly associated with lower CAD risks, and in the summary-level MR, the causal estimates by the pleiotropy-robust MR methods also indicated that higher linoleic acid levels cause a lower risk of CAD. Arachidonic acid showed significant causal estimates for a higher risk of CAD. This study supports the causal effects of certain n-3 and n-6 PUFA types on the risk of CAD.
我们旨在通过孟德尔随机化（MR）分析研究 n-3 和 n-6 多不饱和脂肪酸（PUFA）对冠心病（CAD）风险的因果影响。这项 MR 研究利用了先前全基因组关联研究为各种血清 n-3 和 n-6 PUFA 水平开发的遗传工具。首先，我们在英国生物库数据（n=337129）中计算了欧洲血统个体中 PUFA 遗传易感性的等位基因分数。通过将等位基因分数回归到 CAD 风险，获得了基于等位基因分数的 MR。其次，我们使用 CARDIoGRAMplusC4D 数据进行了 CAD 的汇总水平 MR（n=184305）。基于等位基因分数和汇总水平 MR 分析，较高的基因预测二十碳五烯酸和二十二碳六烯酸水平与 CAD 风险降低显著相关。较高的亚油酸水平的等位基因分数与较低的 CAD 风险显著相关，并且在汇总水平 MR 中，基于多效性稳健 MR 方法的因果估计也表明较高的亚油酸水平可降低 CAD 的风险。花生四烯酸显示出 CAD 风险升高的显著因果估计。本研究支持某些 n-3 和 n-6 PUFA 类型对 CAD 风险的因果影响。
