Promoter Enrichment of Horvath Clock CpG Sites Relative to the Full Illumina 450K Array Background

Epigenetic clocks predict biological age from DNA methylation patterns. The Horvath 2013 multi-tissue clock selected 353 CpG sites on the basis of predictive performance, not functional criteria. Here we report a genomic annotation analysis of these 353 sites against the full Illumina 450K array background (485,512 sites). Clock sites are enriched in gene promoter regions (60.6% vs 28.8%; OR=3.80, 95% CI 3.05–4.74, p<2.2×10⁻¹⁶) and moderately enriched in CpG islands (38.2% vs 30.9%; OR=1.38, 95% CI 1.11–1.72, p=0.004). Because the background is the full array rather than the candidate pool from which the clock was selected, these results describe where clock sites are located and do not establish function. Preprint, not peer reviewed.