Multiomics Data Analysis Identified CpG Sites That Mediate the Impact of Smoking on Cardiometabolic Traits

Understanding the epigenome paths through which smoking contributes to cardiometabolictraits is important for downstream applications. In this study, an SNP-based analytical pipeline wasused to integrate several publicly available datasets in order to identify CpG sites that mediate theimpact of smoking on cardiometabolic traits and to investigate the underlying molecular mechanisms.After applying stringent statistical criteria, 11 CpG sites were detected that showed significantassociation (p< 5x10(-8)) with cardiometabolic traits at both the discovery and replication stages.By integrating eQTL data, I found genes behind a number of these associations. cg05228408 washypomethylated in smokers and contributed to higher blood pressure by lowering the expressionof theCLCN6gene. cg08639339 was hypermethylated in smokers and lowered the metabolic rateby increasing the expression ofRAB29; furthermore, I notedTMEM120Amediated the impact ofsmoking-cg17325771 on LDL, andLTBP3mediated the smoking-cg07029024 effect on heart rate. Thepathway analysis identified processes through which the identified genes impact their traits. Thisstudy provides a list of CpG sites that mediates the impact of smoking on cardiometabolic traits anda framework to investigate the underlying molecular paths using publicly available data.