Deakin University
Browse
craig-geneticand-2020.pdf (2.53 MB)

Genetic and environmental causes of variation in epigenetic aging across the lifespan

Download (2.53 MB)
journal contribution
posted on 2020-01-01, 00:00 authored by S Li, T L Nguyen, E M Wong, P A Dugué, G S Dite, N J Armstrong, Jeffrey CraigJeffrey Craig, K A Mather, P S Sachdev, R Saffery, J Sung, Q Tan, A Thalamuthu, R L Milne, G G Giles, M C Southey, J L Hopper
Background
DNA methylation-based biological age (DNAm age) is an important biomarker for adult health. Studies 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 environmental 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 < 0.02) at different rates (MZ > DZ 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). Similar results were found for another two epigenetic clocks, suggesting that our observations are robust to how DNAm age is measured. In addition, results for the other clocks were consistent with there also being a role for prenatal environmental factors in determining their variation.


Conclusions
Variation 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.

History

Journal

Clinical Epigenetics

Volume

12

Issue

1

Article number

158

Pagination

1 - 12

Publisher

Springer

Location

Berlin, Germany

ISSN

1868-7075

eISSN

1868-7083

Language

eng

Publication classification

C1 Refereed article in a scholarly journal