Although earlier observational studies have investigated the involvement of n-6 polyunsaturated fatty acids (PUFAs) in age-related macular degeneration (AMD), the specific mechanism by which one or more n-6 PUFAs account for this association remains unknown. The study intended to investigate putative causal connections between n-6 PUFAs and AMD using genetic instruments for n-6 PUFAs characteristics performed by mendelian randomization (MR). To produce unconfounded causal estimates, the 2-sample MR technique was utilised. Researchers took genetic variations significantly linked to circulating linoleic acid (LA) and arachidonic acid (AA) from a sample of 8 631 people and applied them to an AMD case–control investigation. For the sensitivity analysis, the weighted median and MR Egger techniques were employed. With an odds ratio (OR) estimate of 0.967 per percentage rise in total fatty acid increase in LA, our MR analysis showed that circulating LA was a causative protective factor for AMD. In contrast, higher genetically predicted circulating AA increased the risk of AMD. Sensitivity analysis revealed no evidence of unknown pleiotropy. The results of several single-nucleotide polymorphism choices and analytic techniques were consistent, indicating the robustness of the causal connections.

The findings provided genetic evidence that circulating LA was responsible for the protective benefits of n-6 PUFAs against the risk of AMD, whereas AA was responsible for the detrimental effects on increased AMD risk.