Fig. 1: The workflow of this EWAS on urate concentrations.

In this study, we included one discovery cohort called 300BCG, DNA methylation (DNAm) and urate data were generated from this cohort. We did the following analyses in our study. First, we explored whether the baseline serum urate was associated with baseline DNA methylation in a sex-specific way by interaction and sex-stratified analysis. Second, we investigated the urate change and performed the EWAS of urate change after BCG. We did the EWAS on both sexes, urate-by-sex interaction EWAS, and sex-stratified EWAS. After obtaining the urate or urate change-associated CpG sites, we annotated these sites with their proximal genes, followed by enrichment analysis and protein-protein interaction analysis. We also linked these CpG sites with gene expression using published eQTM results. Independent cohorts were used to validate the identified CpG sites.