Aslibekyan S, et al. - Researchers performed an epigenome-wide analysis of blood-derived DNA methylation and tumor necrosis factor α (TNF-α) levels and determined if the findings were clinically relevant. In this meta-analysis involving 11,461 participants who experienced 1,895 coronary events, associations of identified methylation loci with gene expression and incident coronary heart disease were determined in follow-up analyses. A total of 4,794 participants comprised the discovery cohort, and 816 participants were included in the replication study. Findings revealed an association of replicated TNF-α–linked cytosine-phosphate-guanine (CpG) sites with 9% to 19% decreased risk of incident coronary heart disease per 10% higher methylation per CpG site. Overall, novel epigenetic links of circulating TNF-α concentration in blood samples were discovered and replicated. Furthermore, these loci were linked to coronary heart disease risk.