Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Department of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
J Clin Endocrinol Metab. 2021 Aug 18;106(9):e3565-e3572. doi: 10.1210/clinem/dgab338.
Although the role of n-6 polyunsaturated fatty acids (PUFAs) in age-related macular degeneration (AMD) has been studied in previous observational studies, the precise manner in which 1 or more n-6 PUFAs account for this relationship remains unclear.
Using genetic instruments for n-6 PUFAs traits implemented through mendelian randomization (MR), we aimed to study possible causal associations between n-6 PUFAs and AMD.
The 2-sample MR method was used to obtain unconfounded causal estimates. We selected genetic variants strongly associated (P < 5 × 10-8) with circulating linoleic acid (LA) and arachidonic acid (AA) from a study involving 8 631 individuals and applied to an AMD case-control study (33 526 participants and 16 144 cases). The weighted median and MR Egger methods were used for the sensitivity analysis.
Our MR analysis suggested that circulating LA was a causal protective factor for AMD, with an odds ratio (OR) estimate of 0.967 (95% CI 0.945 to 0.990; P = .005) per percentage in total fatty acid increase in LA. In contrast, higher genetically predicted circulating AA causally increased the AMD risk (OR = 1.034; 95% CI 1.012 to 1.056; P = .002). Sensitivity analysis provided no indication of unknown pleiotropy. The findings from different single-nucleotide polymorphism selections and analytic methods were consistent, suggesting the robustness of the causal associations.
Our study provided genetic evidence that circulating LA accounted for protective effects of n-6 PUFAs against the risk of AMD, whereas AA was responsible for deleterious effects on higher AMD risk.
尽管 n-6 多不饱和脂肪酸（PUFAs）在年龄相关性黄斑变性（AMD）中的作用已在先前的观察性研究中进行了研究，但 1 种或多种 n-6 PUFAs 如何解释这种关系尚不清楚。
我们使用通过孟德尔随机化（MR）实现的 n-6 PUFAs 特征的遗传工具，旨在研究 n-6 PUFAs 与 AMD 之间可能存在的因果关系。
使用两样本 MR 方法获得无偏因果估计。我们从一项涉及 8631 人的研究中选择与循环亚油酸（LA）和花生四烯酸（AA）强烈相关（P<5×10-8）的遗传变异，并将其应用于 AMD 病例对照研究（33526 名参与者和 16144 例）。加权中位数和 MR Egger 方法用于敏感性分析。
我们的 MR 分析表明，循环 LA 是 AMD 的保护性因果因素，LA 总脂肪酸增加 1%，则 OR 估计值为 0.967（95%CI 0.945 至 0.990；P=0.005）。相比之下，较高的遗传预测循环 AA 会增加 AMD 的发病风险（OR=1.034；95%CI 1.012 至 1.056；P=0.002）。敏感性分析没有表明存在未知的混杂。不同单核苷酸多态性选择和分析方法的结果一致，表明因果关系的稳健性。
我们的研究提供了遗传证据，表明循环 LA 解释了 n-6 PUFAs 对 AMD 风险的保护作用，而 AA 则对更高的 AMD 风险产生有害影响。
