Dataset Information

Reproductive history and blood cell DNA methylation later in life: the Young Finns Study.

ABSTRACT:

Background

Women with a history of complications of pregnancy, including hypertensive disorders, gestational diabetes or an infant fetal growth restriction or preterm birth, are at higher risk for cardiovascular disease later in life. We aimed to examine differences in maternal DNA methylation following pregnancy complications.

Methods

Data on women participating in the Young Finns study (n = 836) were linked to the national birth registry. DNA methylation in whole blood was assessed using the Infinium Methylation EPIC BeadChip. Epigenome-wide analysis was conducted on differential CpG methylation at 850 K sites. Reproductive history was also modeled as a predictor of four epigenetic age indices.

Results

Fourteen significant differentially methylated sites were found associated with both history of pre-eclampsia and overall hypertensive disorders of pregnancy. No associations were found between reproductive history and any epigenetic age acceleration measure.

Conclusions

Differences in epigenetic methylation profiles could represent pre-existing risk factors, or changes that occurred as a result of experiencing these complications.

SUBMITTER: Harville EW

PROVIDER: S-EPMC8690999 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Chronological aging-associated changes in the human DNA methylome are studied by multiple epigenome-wide association studies (EWAS); however, the aging-associated DNAmet changes identified among different age groups and tissues vary and especially the rates of aging-associated alterations in the epigenome during adulthood remain unclear. Here, we further explore and characterize CpG-sites where DNA methylation levels alter at a constant rate during adulthood and are also independent of blood cell type heterogeneity. Results In the study, we observed 1,202 aging-associated CpG-sites (a-CpGs), of which 48% were hypermethylated with advancing age in whole blood with an especially narrow age range (40 - 49 years). Repeatedly reported a-CpGs in ELOVL2, FHL2, PENK and KLF14 were also identified. Regions with aging-associated hypermethylation were enriched to several gene ontology terms (especially on the cluster of developmental processes), while hypomethylated sites showed no enrichment. The genes with a higher number of a-CpG hits were more often hypermethylated. Of the 1,202 aging-associated CpG-sites in the present study, 987 were identified in previous study (Vitality 90+) as differentially methylated also between nonagenarians and young adults in a previous study, and importantly, the directions of changes were identical in the previous and in the present study. Conclusions The set of 987 replicated a-CpGs presented here are altered in strong association with chronological aging in the whole range of adulthood. Consequently, future studies should note the variability of the types of a-CpGs, and the a-CpGs presented here should be dissociated from the environmental-sensitive CpG-sites or from regions that are associated with aging in a non-linear manner due to the accumulation of senescence-related features. This report offers detailed and verified pool of a-CpGs in which DNAmet levels associate linearly with chronological age and of which are different from the non-linearly changing ones.