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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2018.00663

Using Integrative Analysis of DNA Methylation and Gene Expression Data in Multiple Tissue Types to Prioritize Candidate Genes for Drug Development

Qingjie Guo1, 2, Ruonan Zheng3, Jiarui Huang3, Meng He3, Yuhan Wang3, Zonghao Guo3, Liankun Sun1* and  Peng Chen1, 2*
  • 1College of Basic Medical Sciences, Jilin University, China
  • 2Key Laboratory of Pathobiology, Ministry of Education, Jilin University, China
  • 3College of Clinical Medicine, Jilin University, China

Obesity has become a major public health problem which is caused by a combination of genetic and environmental factors. Genome-wide DNA methylation studies had identified that DNA methylation at Cytosine-phosphate-Guanine (CpG) sites associated with obesity. However, subsequent functional investigations were hampered by numerous associated loci. In this study, we applied an integrative analysis approach aiming to prioritize the drug development candidate genes from many associated CpGs. Association data was collected from previous genome-wide DNA methylation studies and combined together using a sample-size-weighted strategy. Gene expression data in adipose tissues and enriched pathways of the affiliated genes were overlapped to shortlist the associated CpGs. The CpGs with the most overlapping evidences were located as the most appropriate CpGs for future studies. Our results revealed that 119 CpGs were associated with the obesity (p<1.03×10-7). Of the affiliated genes, SOCS3 was the only one involved in all enriched pathways and differentially expressed in both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). In conclusion, our integrative analysis is an effective approach in highlighting the DNA methylation of most drug development relevance. SOCS3 may serve as a target for drug development of obesity and its complications.

Keywords: DNA Methylation, Obesity, Association, Gene Expression, CpG

Received: 24 Jul 2018; Accepted: 04 Dec 2018.

Edited by:

Chandravanu Dash, Meharry Medical College, United States

Reviewed by:

Zhenbang Chen, Meharry Medical College, United States
Meenal Gupta, University of Utah, United States  

Copyright: © 2018 Guo, Zheng, Huang, He, Wang, Guo, Sun and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Liankun Sun, College of Basic Medical Sciences, Jilin University, Changchun, 130012, Jilin Province, China, sunlk@jiu.edu.cn
Prof. Peng Chen, College of Basic Medical Sciences, Jilin University, Changchun, 130012, Jilin Province, China, peng_chen@outlook.com