Reproduction, DNA methylation and biological age

Are reproductive characteristics associated with genome-wide DNA methylation and epigenetic age?

Our data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age.

A study of 397 young Filipino women (ages 20-22) observed increasing epigenetic age with an increasing number of pregnancies.

We used data from 2356 non-Hispanic white women (ages 35-74) enrolled in the Sister Study cohort.

Data on reproductive history were ascertained via questionnaire. Of the 2356 women, 1897 (81%) reported at least one live birth. Among parous women, 487 (26%) women reported ever experiencing a pregnancy complication. Three epigenetic clocks (i.e. Hannum, Horvath and Levine) and genome-wide methylation were measured in DNA from whole blood using Illumina's HumanMethylation450 BeadChip. We estimated association β-values and 95% CIs using linear regression.

All three epigenetic clocks showed weak associations between number of births and epigenetic age (per live birth; Hannum: β = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: β = 0.12, 95% CI = -0.04, 0.27, P = 0.14; Levine: β = 0.27, 95% CI = 0.08, 0.45, P = 0.01); however, additional adjustment for current BMI attenuated the associations. Among parous women, a history of abnormal glucose tolerance during pregnancy was associated with increased epigenetic age by the Hannum clock (β = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (β = 1.69; 95% CI = 0.54, 2.84; P < 0.01). In epigenome-wide analysis, increasing parity was associated with methylation differences at 17 CpG sites (Bonferroni corrected P≤ 1.0 × 10-7).

We relied on retrospective recall to ascertain reproductive history and pregnancy complications.

Our findings suggest that parity is associated with small increases in epigenetic age and with DNA methylation at multiple sites in the genome.

This research was supported by the Intramural Research program of the NIH, National Institute of Environmental Health Sciences (Z01-ES049033, Z01-ES049032 and Z01-ES044055). None of the authors have a conflict of interest.

Not applicable.