Dissecting Regulatory Mechanisms Underlying Noncoding GWAS SNPs on 20 Autoimmune Disease

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.