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Dissecting Regulatory Mechanisms Underlying Noncoding GWAS SNPs on 20 Autoimmune Disease

48 Pages Posted: 26 Jan 2019 Publication Status: Review Complete

See all articles by Xiao-Feng Chen

Xiao-Feng Chen

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering; Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Min-Rui Guo

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering; Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Yuan-Yuan Duan

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering; Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Feng Jiang

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering; Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Shan-Shan Dong

Xi'an Jiaotong University (XJTU) - Key Laboratory of Biomedical Information Engineering, Ministry of Education; Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Hlaing Nwe Thynn

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering; Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Cong-Cong Liu

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering; Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Lin Zhang

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering; Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Yan Guo

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering; Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Tie-Lin Yang

Xi'an Jiaotong University (XJTU) - Key Laboratory of Biomedical Information Engineering, Ministry of Education; Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

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Abstract

Over 90% of autoimmune diseases risk variants are located in the noncoding region, leading to great challenge in deciphering the underlying causal functional variants/genes and biological mechanisms. Here we devised an integrative analysis strategy named fGWASAD for identifying not only noncoding functional variants but also gene targets, and underlying biological mechanisms as well as functional roles and clinical implications of gene targets on 20 autoimmune diseases. We demonstrated the credibility of our approach, and further decoded immunologically functional clues for 72.2% of target genes and regulatory mechanisms underlying 71.2% of functional variants. By leveraging pleiotropic effect among target genes, we predicted many candidate drug target genes and new indications for known drugs on several autoimmune diseases. We also suggested the crucial regulatory roles of super enhancers on autoimmune diseases network involving several key master TFs. Together, our analysis provided valuable comprehensive resource for autoimmune diseases, which are freely available online.

Keywords: fGWASAD, autoimmune disease, cell-specific multi-omics, HWCES, noncoding functional variants, Hi-C, QTL, long-range regulation, molecular regulatory mechanisms, drug repurposing

Suggested Citation

Chen, Xiao-Feng and Guo, Min-Rui and Duan, Yuan-Yuan and Jiang, Feng and Dong, Shan-Shan and Thynn, Hlaing Nwe and Liu, Cong-Cong and Zhang, Lin and Guo, Yan and Yang, Tie-Lin, Dissecting Regulatory Mechanisms Underlying Noncoding GWAS SNPs on 20 Autoimmune Disease (January 25, 2019). Available at SSRN: https://ssrn.com/abstract=3322367 or http://dx.doi.org/10.2139/ssrn.3322367
This version of the paper has not been formally peer reviewed.

Xiao-Feng Chen

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering

Xi’an, 710049
China

Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Xi'an
China

Min-Rui Guo

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering

Xi’an, 710049
China

Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Xi'an
China

Yuan-Yuan Duan

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering

Xi’an, 710049
China

Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Xi'an
China

Feng Jiang

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering

Xi’an, 710049
China

Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Xi'an
China

Shan-Shan Dong

Xi'an Jiaotong University (XJTU) - Key Laboratory of Biomedical Information Engineering, Ministry of Education

Xi’an, 710049
China

Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Xi'an
China

Hlaing Nwe Thynn

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering

Xi’an, 710049
China

Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Xi'an
China

Cong-Cong Liu

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering

Xi’an, 710049
China

Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Xi'an
China

Lin Zhang

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering

Xi’an, 710049
China

Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics

Xi'an
China

Yan Guo

Government of the People's Republic of China, Ministry of Education, Key Laboratory of Biomedical Information Engineering ( email )

Xi’an, 710049
China

Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics ( email )

Xi'an
China

Tie-Lin Yang (Contact Author)

Xi'an Jiaotong University (XJTU) - Key Laboratory of Biomedical Information Engineering, Ministry of Education ( email )

Xi’an, 710049
China

Xi'an Jiaotong University (XJTU), School of Life Science and Technology, Institute of Molecular Genetics ( email )

Xi'an
China

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