Omega-3 Fatty Acids as Protective Factors for Age-related Macular Degeneration: Prospective Cohort and Mendelian Randomization Analyses
Abstract
Purpose: Epidemiological studies and clinical trials have reported inconsistent findings regarding the protective role of omega-3 fatty acids in age-related macular degeneration (AMD), we investigated their association in a prospective cohort and examined causality using Mendelian randomization (MR) analyses. Design: Prospective cohort study and two-sample MR analyses. Participants: We included individuals of European descent from UK Biobank with plasma omega-3 and docosahexaenoic acid (DHA) measurement. Our MR analyses used genome-wide association study data on plasma level of omega-3 and DHA (UK Biobank, n=115,006) and AMD (dry, wet, and any) (FinnGen, n=208,690 to 209,122). Methods: Cox regression models was used to assess the association between plasma omega-3/DHA levels and AMD incidence, adjusting for systemic covariates and AMD polygenetic risk score (PRS). Interaction effects of AMD genetic risk (PRS, CFH/ARMS2 genotypes) and plasma omega-3/DHA levels were tested. For MR analyses, we used random-effect inverse-variance weighted (RE-IVW) model as primary model and five other models for sensitivity. Causality between omega-3/DHA and AMD was considered significant if P-values were 0.05). Conclusions: Our prospective cohort and MR analyses both suggested a protective effect of omega-3 and DHA on AMD, supporting the need for further clinical trials to test their effectiveness in AMD prevention and treatment.
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 208,690 participants or records.
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