Research Paper Volume 14, Issue 23 pp 9484—9549

DNA methylation GrimAge version 2

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Figure 1. DNAm GrimAge2. The left panel displays the components of GrimAge2 trained by Cox regression with an elastic net penalty. The elastic net regression model automatically selected the following covariates: chronological age (Age), gender (Female), and ten DNAm based surrogates for smoking pack-years (DNAm PACKYRS), adrenomedullin levels (DNAm ADM), beta-2 microglobulin (DNAm B2M), cystatin C (DNAm Cystatin C), growth differentiation factor 15 (DNAm GDF-15), leptin (DNAm Leptin), log-scale high sensitivity C-reactive protein (DNAm logCRP), log-scale hemoglobin A1C (DNAm logA1C), plasminogen activation inhibitor 1 (DNAm PAI-1), tissue inhibitor metalloproteinase 1 (DNAm TIMP-1). The linear combination of the covariate values XTβ was linearly transformed to be in units of years, as described in the bottom. Technically speaking, DNAm GrimAge2 is an epigenetic clock for mortality risk. Metaphorically speaking, it estimates biological age in units of years. The right panel displays selective factors including diet, lifestyle and clinical biomarkers that were significantly associated with age acceleration measure of GrimAge2 or age-adjusted DNAm biomarkers underlying GrimAge2 in our downstream analysis.