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Hum Reprod. 2019 Oct 2;34(10):1965-1973. doi: 10.1093/humrep/dez149.

Reproduction, DNA methylation and biological age.

Author information

1
Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
2
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
3
Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

Abstract

STUDY QUESTION:

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

SUMMARY ANSWER:

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

WHAT IS KNOWN ALREADY:

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

STUDY DESIGN, SIZE, DURATION:

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

PARTICIPANTS/MATERIALS, SETTING, METHODS:

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.

MAIN RESULTS AND THE ROLE OF CHANCE:

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).

LIMITATIONS, REASONS FOR CAUTION:

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

WIDER IMPLICATIONS OF THE FINDINGS:

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

STUDY FUNDING/COMPETING INTEREST(S):

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.

TRIAL REGISTRATION NUMBER:

Not applicable.

KEYWORDS:

DNA methylation; biological age; epigenetic clock; parity; pregnancy complications

PMID:
31600381
DOI:
10.1093/humrep/dez149

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