Epigenome-wide CpG methylation was profiled using either Illumina HumanMethylation450 BeadChip (450K) (San Diego, CA, USA) (57.2% of the sample) or Illumina HumanMethylation EPIC BeadChip (EPIC) (San Diego, CA, USA) (42.8% of the sample) in VACS. All samples were processed at the Yale Center for Genomic Analysis [27 (link)]. The same QC criteria were used as in our previous studies [27 (link),30 (link),31 (link)]. We retrieved methylation raw data using the minfi R package (version 1.18.1) and all probes were normalized. Methylation-inferred sex agreed with self-reported sex (100% of the sample was male).
Epigenetic age was estimated using four epigenetic clocks, the Horvath [10 (link)], Hannum [11 (link)], Pheno [12 (link)], and Grim [13 (link)] clocks. EAA was defined as the residuals of regressing epigenetic age on chronological age, which was applied to test the mediation effect on the relationship between IDUHCV and mortality risk [10 (link),14 (link)]. We also calculated the mean difference in EAA between IDU+HCV+ and IDU-HCV- and denoted it as the median difference of EAA (MDEAA).
Epigenetic age was estimated using four epigenetic clocks, the Horvath [10 (link)], Hannum [11 (link)], Pheno [12 (link)], and Grim [13 (link)] clocks. EAA was defined as the residuals of regressing epigenetic age on chronological age, which was applied to test the mediation effect on the relationship between IDUHCV and mortality risk [10 (link),14 (link)]. We also calculated the mean difference in EAA between IDU+HCV+ and IDU-HCV- and denoted it as the median difference of EAA (MDEAA).
