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
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
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
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
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
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
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
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
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
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
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.
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.
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