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Smoking-induced DNA hydroxymethylation signature is less pronounced than true DNA methylation: The population-based KORA Fit cohort
Biomolecules 14:662 (2024)
Despite extensive research on 5-methylcytosine (5mC) in relation to smoking, there has been limited exploration into the interaction between smoking and 5-hydroxymethylcytosine (5hmC). In this study, total DNA methylation (5mC+5hmC), true DNA methylation (5mC) and hydroxymethylation (5hmC) levels were profiled utilizing conventional bisulphite (BS) and oxidative bisulphite (oxBS) treatment, measured with the Illumina Infinium Methylation EPIC BeadChip. An epigenome-wide association study (EWAS) of 5mC+5hmC methylation revealed a total of 38,575 differentially methylated positions (DMPs) and 2023 differentially methylated regions (DMRs) associated with current smoking, along with 82 DMPs and 76 DMRs associated with former smoking (FDR-adjusted p < 0.05). Additionally, a focused examination of 5mC identified 33 DMPs linked to current smoking and 1 DMP associated with former smoking (FDR-adjusted p < 0.05). In the 5hmC category, eight DMPs related to current smoking and two DMPs tied to former smoking were identified, each meeting a suggestive threshold (p < 1 × 10-5). The substantial number of recognized DMPs, including 5mC+5hmC (7069/38,575, 2/82), 5mC (0/33, 1/1), and 5hmC (2/8, 0/2), have not been previously reported. Our findings corroborated previously established methylation positions and revealed novel candidates linked to tobacco smoking. Moreover, the identification of hydroxymethylated CpG sites with suggestive links provides avenues for future research.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Dna Methylation ; Illumina Infinium Methylation Epic Beadchip ; Differentially Methylated Positions (dmps) ; Differentially Methylated Regions (dmrs) ; Hydroxymethylation ; Smoking; 5-hydroxymethylcytosine; 5-methylcytosine
ISSN (print) / ISBN
2218-273X
e-ISSN
2218-273X
Journal
Biomolecules
Quellenangaben
Volume: 14,
Issue: 6,
Article Number: 662
Publisher
MDPI
Publishing Place
Basel
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology II (EPI2)
Grants
China Scholarship Council
Munich Center of Health Sciences (MC-Health) at Lud-wig-Maximilians-Universitaet, LMUinnovativ
State of Bavaria
German Federal Ministry of Education and Research (BMBF)
Helmholtz Zentrum Muenchen-German Research Center for Environmental Health
Munich Center of Health Sciences (MC-Health) at Lud-wig-Maximilians-Universitaet, LMUinnovativ
State of Bavaria
German Federal Ministry of Education and Research (BMBF)
Helmholtz Zentrum Muenchen-German Research Center for Environmental Health