Williams DM, et al. - Researchers performed two-sample Mendelian randomization analyses to investigate whether Alzheimer disease (AD) risk would be lower in individuals with lifelong, genetically predicted increases in concentrations of 4 circulating antioxidants that are modifiable by diet. The ultimate goal was to investigate if long-term circulating antioxidant exposure plays a role in AD etiology. Single-nucleotide polymorphisms (SNPs) that determine variation in circulating ascorbate (vitamin C), β-carotene, retinol (vitamin A), and urate were identified from published genetic association studies. The investigators used data from a genome-wide association study of late-onset AD cases and controls (n=17,008 and 37,154, respectively) to obtain statistics for genotype associations with AD risk for each set of SNP data. In order to evaluate the four sets of SNP-exposure and SNP-AD associations, the primary methods used included ratio-of-coefficients and inverse-variance-weighted meta-analyses. No reduction in AD risk was suggested in relation to higher exposure to ascorbate, β-carotene, retinol, or urate. There was little evidence to suggest that pleiotropy had biased results.