Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 5 May 2023 / Approved: 6 May 2023 / Online: 6 May 2023 (09:56:37 CEST)

A peer-reviewed article of this Preprint also exists.

Nikpay, M. Multiomics Data Analysis Identified CpG Sites That Mediate the Impact of Smoking on Cardiometabolic Traits. Epigenomes 2023, 7, 19. https://doi.org/10.3390/epigenomes7030019 Nikpay, M. Multiomics Data Analysis Identified CpG Sites That Mediate the Impact of Smoking on Cardiometabolic Traits. Epigenomes 2023, 7, 19. https://doi.org/10.3390/epigenomes7030019

Abstract

Understanding epigenome paths through which smoking contributes to cardiometabolic traits is important for downstream applications. In this study, I used a SNP-based analytical pipeline to integrate several publicly available datasets and identify CpG sites that mediate the impact of smoking on cardiometabolic traits. After applying stringent statistical criteria, 11 CpG sites were detected that showed significant association (P<5e-8) with cardiometabolic traits at both discovery and replication stage. By integrating eQTL data, I identified genes behind a number of these associations. cg05228408 was hypomethylated in smokers and contributed to higher blood pressure by lowering the expression of CLCN6 gene. cg08639339 was hypermethylated in smokers and lowered metabolic rate by increasing the expression of RAB29; furthermore, I noted TMEM120A mediated the impact of smoking-cg17325771 on LDL, and LTBP3 mediated the smoking-cg07029024 effect on heart rate. This study provides a list of CpG sites that mediates the impact of smoking on cardiometabolic traits and a framework to investigate epigenome path through which a lifestyle habit modifies disease risks.

Keywords

smoking,; DNA methylation; cardiometabolic traits; mendelian randomization

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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