4.7 Article

Causal Effects of N-6 Polyunsaturated Fatty Acids on Age-related Macular Degeneration: A Mendelian Randomization Study

Journal

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 106, Issue 9, Pages E3565-E3572

Publisher

ENDOCRINE SOC
DOI: 10.1210/clinem/dgab338

Keywords

N-6 polyunsaturated fatty acids; linoleic acid; arachidonic acid; age-related macular degeneration; Mendelian randomization

Funding

  1. National Natural Science Foundation of China [81870641, 81970779, 82070939]
  2. Key Research and Development Project of Zhejiang Province [2020C03035]

Ask authors/readers for more resources

The study found that circulating linoleic acid (LA) accounted for the protective effects of n-6 PUFAs against age-related macular degeneration (AMD), while arachidonic acid (AA) was associated with an increased risk of AMD.
Context: 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. Objective: 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. Methods: The 2-sample MR method was used to obtain unconfounded causal estimates. We selected genetic variants strongly associated (P < 5 x 10(-8)) with circulating linoleic acid (LA) and arachidonic acid (AA) from a study involving 8631 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. Results: 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. Conclusion: 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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available