Abstract
Individuals differ in when and how quickly they experience puberty, and these differences in pubertal development are associated with lifelong health and mortality. We conducted sex-specific epigenome-wide association analyses of salivary DNA-methylation (DNAm) samples from ~ 3500 adolescents and identified 373 DNAm sites significantly associated with pubertal age, pace of pubertal development, and/or onset of early puberty by age 9. These DNAm signals converged with results from previous genomic and transcriptomic studies of puberty and with pan-mammalian epigenomic studies of age. Genomic annotations and trait enrichment results implicate child maltreatment and toxicant exposures as relevant for puberty. We developed a novel DNAm biomarker of pubertal age that was consistently associated with earlier age at menarche across three adolescent cohorts. Saliva DNAm is sensitive to signatures of pubertal development and suggests molecular links between reproductive maturation and both embryonic development and biological aging across species.