Abstract
Purpose :
Unsaturated fatty acids (FA) have been extensively studied for their role in age-related macular degeneration (AMD), yet evidence from epidemiological studies and randomized controlled trials remains inconclusive. We assessed the impact of genetically predicted unsaturated FA on AMD using mendelian randomization (MR) approaches.
Methods :
Leveraging extensive European-sourced genome-wide association study data, including 115,006 samples from UK Biobank for FA, 14,034 cases with 91,214 controls for early AMD, as well as 16,444 cases and 17832 controls from the International AMD Genomics Consortium for advanced AMD (including geographic atrophy, choroidal neovascularization, intermediate AMD), we assessed the potential causal relationships of 6 circulating unsaturated FA concentrations, including polyunsaturated FA (PUFA), omega-3, docosahexaenoic acid, omega-6, linoleic acid, monounsaturated FA (MUFA), with early AMD and advanced AMD using two-sample MR approach. We employed random-effects inverse-variance weighted (IVW) as main analyses, and MR-Egger, MR-weighted median, and MR-weighted mode as sensitivity analyses. A false detection rate-adjusted P-value below 0.05 in MR-IVW, MR-weighted median, and MR-weighted mode with consistent effect estimates in MR-Egger indicated statistical significance.
Results :
We identified 40 to 88 SNPs as instrumental variables for the 6 unsaturated FA traits and their ratios. Higher genetically predicted MUFA/total FA ratio (early AMD: OR, 0.84; 95%CI, 0.76-0.92; adjusted P=5.28×10-4; advanced AMD: OR, 0.79; 95%CI, 0.67-0.93; adjusted P= 6.68×10-3 ) and MUFA/PUFA ratio (early AMD: OR, 0.82; 95%CI, 0.74-0.90; adjusted P= 9.40×10-5; advanced AMD: OR, 0.81; 95%CI, 0.68-0.97; adjusted P= 0.025) correlated with reduced risk of both early AMD and advanced AMD. MUFA concentration was associated with lower risk of early AMD (OR, 0.79; 95%CI, 0.72-0.86; adjusted P=1.10×10-7), but its association with advanced AMD was only significant in IVW model (OR, 0.77; 95%CI, 0.64-0.93; adjusted P=0.012). No significant association was found between other unsaturated FA types and AMD (all P>0.05).
Conclusions :
Our study suggests potentially protective effect of higher circulating MUFA, particularly in its ratio to total FA and PUFA, against AMD. This underscores the need for further clinical trials to evaluate them as preventive treatments.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.