Differential Regulation of the DNA Methylome in Adults Born During the Great Chinese Famine in 1959-1961

Extensive epidemiological studies have established the association between exposure to early-life adversity and health status diseases in adults. Epigenetic regulation is considered as a key mediator for this phenomenon but analysis on humans sparse. The Great Chinese Famine lasting from 1958 1961 natural string of disasters offering precious opportunity elucidating underlying epigenetic mechanism long-term effect early adversity. Using high-throughput array platform DNA methylome profiling, we conducted an epigenome-wide study famine adults born during 1959-1961 compared unexposed subjects 1963-1964. single CpG site whole epigenome revealed predominant pattern decreased methylation levels associated with fetal famine. Four sites were detected p <1e-06 (linked EHMT1, CNR1, UBXN7 ESM1 genes), 16 CpGs 1e-06< <1e-05 158 1e-05< <1e-04, hypomethylation. Functional annotation genes their enriched biological pathways mainly involved neurodevelopment, neuropsychological disorders metabolism. Multiple two top-rank differentially methylated regions harbouring RNF39 chromosome 6 PTPRN2 7, both showing stress-related conditions. In conclusion, results provide new clues embedding its impacts adult health. Funding Statement: This was financially supported by Independent Research Fund Denmark grant number DFF – 6110-00114. Declaration Interests: None declared. Ethics Approval approved Ethics Committee Qingdao CDC. Written informed consents obtained all participants.