Leukocyte Composition Change Accounts for Most Apparent Ten-Year DNA Methylation Drift in Blood: A Two-Cohort Longitudinal Analysis

Analysis code and derived result tables supporting a two-cohort longitudinal reanalysis testing whether decade-scale change in a blood-referenced DNA methylation burden score survives adjustment for concurrent change in leukocyte composition. Cohorts are the Danish Longitudinal Study of Aging Twins (GEO accession GSE73115; 86 paired participants, 120-month interval, Illumina 450K, whole blood) and the Health, Aging and Body Composition study (GSE130748; 17 paired participants, Illumina EPIC, buffy coat). The cell-composition reference is built from purified leukocyte fractions (GSE35069). The 48-locus burden panel specification (probe identifiers, GRCh38 coordinates, direction, reference means, scale constant, locus weights); a standalone reimplementation of the burden score; the per-locus change-in-beta table for both cohorts; the storage/centrality regression with boundary-sensitivity arms; the replicate-derived technical noise floor; a probe-set disjointness check confirming that composition estimation and burden scoring share no probes; and the two manuscript figures with the code that generates them. All primary methylation data are publicly available at the GEO accessions above. Code is released under the MIT License; data, figures, and documentation under CC BY 4.0. The author is the founder, CEO, and CSO of Alercell, Inc., which develops DNA methylation-based diagnostics. The findings constrain the interpretation of blood-based DNA methylation measures generally, including approaches under development at Alercell.