Differential regulation of the DNA methylome in adults born during the Great Chinese Famine in 1959-1961
Background: Extensive epidemiological studies have established the association between exposure to early-life adversity and health status and diseases in adults. Epigenetic regulation is considered as a key mediator for this phenomenon but analysis on humans is sparse. The Great Chinese Famine lasting from 1958 to 1961 is a natural string of disasters offering a precious opportunity for elucidating the underlying epigenetic mechanism of the long-term effect of early adversity. Methods: Using a high-throughput array platform for DNA methylome profiling, we conducted a case-control epigenome-wid... Mehr ...
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Dokumenttyp: | Artikel |
Erscheinungsdatum: | 2022 |
Verlag/Hrsg.: |
Academic Press
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Schlagwörter: | Fetal adversity / Chinese famine / DNA methylation / Association / PRENATAL EXPOSURE / BLOOD-PRESSURE / DUTCH FAMINE / EARLY-LIFE / SCHIZOPHRENIA / CONSEQUENCES / METHYLATION / MUTATIONS / RISK / POPULATION / 11832 Microbiology and virology / 1184 Genetics / developmental biology / physiology / 3142 Public health care science / environmental and occupational health |
Sprache: | Englisch |
Permalink: | https://search.fid-benelux.de/Record/base-26675845 |
Datenquelle: | BASE; Originalkatalog |
Powered By: | BASE |
Link(s) : | http://hdl.handle.net/10138/339568 |
Background: Extensive epidemiological studies have established the association between exposure to early-life adversity and health status and diseases in adults. Epigenetic regulation is considered as a key mediator for this phenomenon but analysis on humans is sparse. The Great Chinese Famine lasting from 1958 to 1961 is a natural string of disasters offering a precious opportunity for elucidating the underlying epigenetic mechanism of the long-term effect of early adversity. Methods: Using a high-throughput array platform for DNA methylome profiling, we conducted a case-control epigenome-wide association study on early-life exposure to Chinese famine in 79 adults born during 1959-1961 and compared to 105 unexposed subjects born 1963-1964. Results: The single CpG site analysis of whole epigenome revealed a predominant pattern of decreased DNA methylation levels associated with fetal exposure to famine. Four CpG sites were detected with p < 1e-06 (linked to EHMT1, CNR1, UBXN7 and ESM1 genes), 16 CpGs detected with 1e-06 < p < 1e-05 and 157 CpGs with 1e-05 < p < 1e-04, with a predominant pattern of hypomethylation. Functional annotation to genes and their enriched biological pathways mainly involved neurodevelopment, neuropsychological disorders and metabolism. Multiple sites analysis detected two top-rank differentially methylated regions harboring RNF39 on chromosome 6 and PTPRN2 on chromosome 7, both showing epigenetic association with stress-related conditions. Conclusion: Early-life exposure to famine could mediate DNA methylation regulations that persist into adulthood with broad impacts in the activities of genes and biological pathways. Results from this study provide new clues to the epigenetic embedding of early-life adversity and its impacts on adult health. ; Peer reviewed