Higher plasma vitamin D levels are not causally associated with less age‐related macular degeneration

Abstract

PURPOSE: Higher levels of plasma 25-hydroxyvitamin D have been associated with a lower risk of age-related macular degeneration (AMD). We investigated observational and potential causal associations of plasma 25-hydroxyvitamin D with the risk of AMD in two large contemporary population-based prospective studies and a genetic case-control consortium. METHODS: Observationally, we studied 25 445 individuals with measured baseline plasma 25-hydroxyvitamin D (536 incident AMD events) in the Copenhagen General Population Study (CGPS) and 372 477 individuals (7842 incident AMD events) in the UK Biobank using Cox regression analysis for hazard ratios. Causally, we studied 107 793 individuals (1474 incident AMD events) in the CGPS, 406861 individuals (9183 incident AMD events) in the UK Biobank and 31 858 individuals (17 411 AMD cases) in the International AMD Genomics Consortium with genetic variants leading to life-long elevated plasma 25-hydroxyvitamin D. These genetic variants were combined to plasma 25-hydroxyvitamin D-increasing unweighted and weighted allele scores and genetic associations to AMD risk were tested using Cox regression and logistic regression for hazard ratios and odds ratios. RESULTS: Observationally, higher plasma 25-hydroxyvitamin D was associated with higher AMD risk in CGPS and lower risk in UK Biobank. Genetically, each increase in the 25-hydroxyvitamin D-increasing weighted CGPS allele score was associated with a hazard ratio of 1.01 (95% confidence interval: 1.00-1.02) in CGPS, with similar results in the other studies. CONCLUSION: These findings do not support a causal role of plasma 25-hydroxyvitamin D in the risk of AMD.