Although no significant interaction between PRSs and metabolites was detected after multiple testing correction (Fig. 2a and Supplementary Tables 13 and 14), we identified eight significant interactions between individual AD/ADRD variants, including those mapped to ABCA1, APP, ADAMTS1, CTSH and USP6NL, and metabolites in relation to dementia risk with an FDR < 0.05 (Fig. 2a,b, Supplementary Fig. 5 and Supplementary Table 15). This evidence concerns the gene CTSH and Alzheimer disease.