Integrative analysis identified mediation effects of lncRNAs on the correlations between methylation and mRNA

Xing-Bo Mo; Long-Fei Wu; Xiao-Ming Cai; Zai-Xiang Tang; Xin Lu; Yong-Hong Zhang; Fei-Yan Deng; Shu-Feng Lei

doi:10.1016/j.biocel.2018.09.005

Integrative analysis identified mediation effects of lncRNAs on the correlations between methylation and mRNA

Int J Biochem Cell Biol. 2018 Nov:104:66-72. doi: 10.1016/j.biocel.2018.09.005. Epub 2018 Sep 15.

Authors

Xing-Bo Mo¹, Long-Fei Wu¹, Xiao-Ming Cai¹, Zai-Xiang Tang¹, Xin Lu¹, Yong-Hong Zhang², Fei-Yan Deng¹, Shu-Feng Lei³

Affiliations

¹ Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu 215123, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, PR China.
² Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, PR China.
³ Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu 215123, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, PR China. Electronic address: leisf@suda.edu.cn.

PMID: 30227253
DOI: 10.1016/j.biocel.2018.09.005

Abstract

The aim of this study was to construct DNA methylation-lncRNA-mRNA interaction trios in peripheral blood mononuclear cells. We first conducted eQTL analyses using genome-wide methylation, lncRNA and mRNA expression data from 43 Chinese females. Next, causal inference test (CIT) was used to detect the lncRNA mediation effects on methylation and mRNA. Methylation-lncRNA cis-eQTL analysis identified 11 significant cis-methylation-lncRNA pairs. Combined with the results from the next lncRNA-mRNA eQTL and methylation-mRNA eQTL analyses, the 11 significant pairs and their corresponding 11,204 target e-mRNAs formed 12,245 trios. Further CIT identified six lncRNAs as mediators in regulating the corresponding pairs between methylation and mRNA. This study detected lncRNAs with mediation effects on the correlations between DNA methylations and a large number of mRNAs.

Keywords: Causal inference test; DNA methylation; Expression; Integrative analysis; Mediation; PBMC; Regulatory; eQTL; lncRNA; mRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computational Biology*
DNA Methylation*
Female
Humans
Quantitative Trait Loci / genetics
RNA, Long Noncoding / genetics*
RNA, Messenger / genetics

Substances

RNA, Long Noncoding
RNA, Messenger