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 one 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 two-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% confidence interval [CI] 0.945 to 0.990; P = 0.005) 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 = 0.002). 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.
Kai Wang, Yueyang Zhong, Fangkun Yang, Chenyang Hu, Xin Liu, Yanan Zhu, Ke Yao