Figure 2. The Figure shows the cross-lagged model used to examine longitudinal associations between DNAm age residuals (Hannum or Horvath) and biological variables of interest (MetS, lab-based WBC measurement, CRP levels, CD4/CD8 T-cell ratio). Measures of each biological marker were residualized on age and sex for all analyses. DNAm age residuals at each time point were generated by regressing raw DNAm age estimates on age, sex, estimated WBCs (CD4-T, CD8-T, NK, b cells, monocytes) from the respective time point, and the top two ancestry PCs and saving the unstandardized residuals from this equation. For analyses predicting estimated CD4/CD8 ratios, DNAm age residuals were calculated by regressing raw DNAm age estimates on age, sex, and the top two ancestry PCs (but not on estimated WBCs as these were the focus of this analysis).