Smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic traits
- PDF / 1,211,918 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 1 Downloads / 229 Views
Open Access
RESEARCH
Smoking‑related changes in DNA methylation and gene expression are associated with cardio‑metabolic traits Silvana C. E. Maas1,2, Michelle M. J. Mens1, Brigitte Kühnel3,4, Joyce B. J. van Meurs5, André G. Uitterlinden1,5, Annette Peters3,4,6,7, Holger Prokisch8, Christian Herder9,10,11, Harald Grallert4, Sonja Kunze3,4, Melanie Waldenberger3,4,6, Maryam Kavousi1, Manfred Kayser2 and Mohsen Ghanbari1*
Abstract 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. Keywords: Cardio-metabolic traits, Epigenetics, DNA methylation, Gene expression, Smoking
*Correspondence: [email protected] 1 Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, 3015 GB Rotterdam, The Netherlands Full list of author information is available at the end of the article
Background Tobacco smoking is a major modifiable risk factor for premature de
Data Loading...
