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Implementing a method for studying longitudinal DNA methylation variability in association with age.

ABSTRACT: Interindividual variability of DNA methylation is a mechanism of the epigenetic drift in aging. Studies on cross-sectional data have discovered a change in methylation variability in association with age. However, thus far, no method explored DNA methylation variability in longitudinal data, which was the aim of this study. First, we performed a simulation study to explore methods for estimating methylation variability in longitudinal data. Second, an epigenome-wide association study (EWAS) on 1011 longitudinal samples (385 individuals followed up to 18 years) was performed to identify age-varying methylation sites using these methods. Following Breusch-Pagan test of heteroscedasticity, we showed that a linear regression model, where the residuals were used in a mixed effect model with a random intercept, properly estimated the change of interindividual variability over time. Our EWAS identified 570 CpG sites where methylation variability was significantly associated with age (P < 1.3 × 10^-7). Gene regions of identified loci were enriched in nervous system development functions. In conclusion, we provide a method for analyzing methylation variability in longitudinal data and further identified age-varying methylation loci in a longitudinal analysis using these methods.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6291263 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Implementing a method for studying longitudinal DNA methylation variability in association with age.

Wang Yunzhang Y Pedersen Nancy L NL Hägg Sara S

Epigenetics 20181002 8

Interindividual variability of DNA methylation is a mechanism of the epigenetic drift in aging. Studies on cross-sectional data have discovered a change in methylation variability in association with age. However, thus far, no method explored DNA methylation variability in longitudinal data, which was the aim of this study. First, we performed a simulation study to explore methods for estimating methylation variability in longitudinal data. Second, an epigenome-wide association study (EWAS) on 1 ...[more]

PMID: 30251590

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Project description:BackgroundDNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation.ObjectivesWe examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006; Cincinnati, Ohio).MethodsWe quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (n=266) and peripheral leukocytes at 12 years of age (n=160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children's age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999-2002; Boston, Massachusetts) to replicate significant associations.ResultsAfter adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, q<0.05). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children's age.DiscussionIn these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. https://doi.org/10.1289/EHP10118.

Dataset Information

Implementing a method for studying longitudinal DNA methylation variability in association with age.

Publications

Implementing a method for studying longitudinal DNA methylation variability in association with age.

Similar Datasets

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