Causes of variation in epigenetic aging across the lifespan

Abstract

BackgroundDNA methylation-based biological age (DNAm age) is potentially an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its causes of variation. We investigated these causes across the lifespan. MethodsWe pooled genome-wide DNA methylation data for 4,217 people aged 0-92 years from 1,871 families. DNAm age was calculated using the Horvath epigenetic clock. We estimated familial correlations in DNAm age for monozygotic (MZ) twin, dizygotic (DZ) twin, sibling, parent-offspring, and spouse pairs by cohabitation status. Genetic and environmental variance component models were fitted and compared. ResultsTwin pair correlations were -0.12 to 0.18 around birth, not different from zero (all P>0.29). For all pairs of relatives, their correlations increased with time spent living together (all PDZ and siblings>parent-offspring; P<0.001) and decreased with time spent living apart (P=0.02) at similar rates. These correlation patterns were best explained by cohabitation-dependent shared environmental factors, the effects of which were 1.41 (95% confidence interval [CI], 1.16 to 1.66) times greater for MZ pairs than for DZ and sibling pairs, and the latter were 2.03 (95% CI, 1.13 to 9.47) times greater than for parent-offspring pairs. Genetic factors explained 13% (95% CI, -10% to 35%) of variation (P=0.27). ConclusionVariation in DNAm age is mostly caused by environmental factors, including those shared to different extents by relatives while living together and whose effects persist into old age. The equal environment assumption of the classic twin study might not hold for epigenetic aging.