Genetic and environmental causes of variation in epigenetic aging across the lifespan
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RESEARCH
Genetic and environmental causes of variation in epigenetic aging across the lifespan Shuai Li1,2,3, Tuong L. Nguyen1, Ee Ming Wong3,4, Pierre‑Antoine Dugué1,3,5, Gillian S. Dite1, Nicola J. Armstrong6, Jeffrey M. Craig7, Karen A. Mather8,9, Perminder S. Sachdev8,9, Richard Saffery10, Joohon Sung11, Qihua Tan12, Anbupalam Thalamuthu8, Roger L. Milne1,3,5, Graham G. Giles1,3,5, Melissa C. Southey3,4,5 and John L. Hopper1*
Abstract Background: DNA methylation-based biological age (DNAm age) is an important biomarker for adult health. Stud‑ ies in specific age ranges have found widely varying results about its genetic and environmental causes of variation. However, these studies are not able to provide a comprehensive view of the causes of variation over the lifespan. Results: In order to investigate the genetic and environmental causes of DNAm age variation across the lifespan, we pooled genome-wide DNA methylation data for 4217 people aged 0–92 years from 1871 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 environ‑ mental variance components models were fitted and compared. We found that twin 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 P DZ and siblings > parent–offspring; P
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