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Lai, L. ; Matias-Garcia, P.R. ; Kretschmer, A. ; Gieger, C. ; Wilson, R. ; Linseisen, J.* ; Peters, A. ; Waldenberger, M.

Smoking-induced DNA hydroxymethylation signature is less pronounced than true DNA methylation: The population-based KORA Fit cohort

Biomolecules 14:662 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Biomolecules
Quellenangaben Band: 14, Heft: 6, Seiten: , Artikelnummer: 662 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Förderungen 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