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Maas, S.C.E.* ; Mens, M.M.J.* ; Kühnel, B. ; van Meurs, J.B.J.* ; Uitterlinden, A.G.* ; Peters, A. ; Prokisch, H. ; Herder, C.* ; Grallert, H. ; Kunze, S. ; Waldenberger, M. ; Kavousi, M.* ; Kayser, M.* ; Ghanbari, M.*

Smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic traits.

Clin. Epigenet. 12:157 (2020)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
Background Tobacco smoking is a well-known modifiable risk factor for many chronic diseases, including cardiovascular disease (CVD). One of the proposed underlying mechanism linking smoking to disease is via epigenetic modifications, which could affect the expression of disease-associated genes. Here, we conducted a three-way association study to identify the relationship between smoking-related changes in DNA methylation and gene expression and their associations with cardio-metabolic traits. Results We selected 2549 CpG sites and 443 gene expression probes associated with current versus never smokers, from the largest epigenome-wide association study and transcriptome-wide association study to date. We examined three-way associations, including CpG versus gene expression, cardio-metabolic trait versus CpG, and cardio-metabolic trait versus gene expression, in the Rotterdam study. Subsequently, we replicated our findings in The Cooperative Health Research in the Region of Augsburg (KORA) study. After correction for multiple testing, we identified both cis- and trans-expression quantitative trait methylation (eQTM) associations in blood. Specifically, we found 1224 smoking-related CpGs associated with at least one of the 443 gene expression probes, and 200 smoking-related gene expression probes to be associated with at least one of the 2549 CpGs. Out of these, 109 CpGs and 27 genes were associated with at least one cardio-metabolic trait in the Rotterdam Study. We were able to replicate the associations with cardio-metabolic traits of 26 CpGs and 19 genes in the KORA study. Furthermore, we identified a three-way association of triglycerides with two CpGs and two genes (GZMA; CLDND1), and BMI with six CpGs and two genes (PID1; LRRN3). Finally, our results revealed the mediation effect of cg03636183 (F2RL3), cg06096336 (PSMD1), cg13708645 (KDM2B), and cg17287155 (AHRR) within the association between smoking and LRRN3 expression. Conclusions Our study indicates that smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic risk factors. These findings may provide additional insights into the molecular mechanisms linking smoking to the development of CVD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cardio-metabolic Traits ; Epigenetics ; Dna Methylation ; Gene Expression ; Smoking; Coronary-heart-disease; C-reactive Protein; Cardiovascular Risk; F2rl3 Methylation; Tobacco Smoking; Signatures; Mortality; Epidemiology; Predictor; Receptor
ISSN (print) / ISBN 1868-7075
e-ISSN 1868-7083
Zeitschrift Clinical Epigenetics
Quellenangaben Band: 12, Heft: 1, Seiten: , Artikelnummer: 157 Supplement: ,
Verlag Springer
Verlagsort Berlin : Heidelberg
Begutachtungsstatus Peer reviewed
Förderungen German Federal Ministry of Education and Research
Erasmus University, Rotterdam
Netherlands Organization for the Health Research and Development (ZonMw)
Research Institute for Diseases in the Elderly (RIDE)
Ministry of Education, Culture and Science
Ministry for Health, Welfare and Sports
European Commission (DG XII)
Municipality of Rotterdam
Genetic Laboratory of the Department of Internal Medicine, Erasmus MC
Netherlands Organization for Scientific research (NWO)
Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research
State of Bavaria
Munich Center of Health Sciences (MC-Health), Ludwig-MaximiliansUniversitat, Munich, Germany, as part of LMUinnovativ
Ministry of Culture and Science of the State of North Rhine-Westphalia
German Federal Ministry of Health
Erasmus Medical Center, Rotterdam