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

作者: Silvana C. E. Maas , Michelle M. J. Mens , Brigitte Kühnel , Joyce B. J. van Meurs , André G. Uitterlinden

DOI: 10.1186/S13148-020-00951-0

关键词:

摘要: Background: Tobacco smoking is a well-known modifable risk factor for many chronic diseases, including cardiovascular disease (CVD). One of the proposed underlying mechanism linking to via epigenetic modifcations, which could afect expression disease-associated genes. Here, we conducted three-way association study identify relationship between smoking-related changes in DNA methylation and gene and their associations with cardio-metabolic traits. Results: We selected 2549 CpG sites 443 probes associated current versus never smokers, from largest epigenome-wide association study transcriptome-wide date. examined three-way associations, expression, trait CpG, Rotterdam study. Subsequently, replicated our fndings The Cooperative Health Research Region Augsburg (KORA) After correction multiple testing, identifed both cis- trans-expression quantitative (eQTM) blood. Specifcally, found 1224 smoking-related CpGs at least one probes, 200 gene expression be CpGs. Out these, 109 27 genes were associated Study. were able replicate associations with traits 26 19 KORA Furthermore, triglycerides two (GZMA; CLDND1), BMI six (PID1; LRRN3). Finally, results revealed mediation efect cg03636183 (F2RL3), cg06096336 (PSMD1), cg13708645 (KDM2B), cg17287155 (AHRR) within LRRN3 expression. Conclusions: Our indicates that are factors. These may provide additional insights into molecular mechanisms linking development CVD.

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