Genome-wide association studies (GWASs) have unraveled thousands of susceptible variants associated with tens of different autoimmune diseases. These associations have accelerated discovery of new biological mechanisms insight underlying disease etiologies as well as clinical drug development. However, over 90% GWAS susceptible variants are located in the noncoding region, leading to great challenge in deciphering the underlying causal functional variants/genes and biological mechanisms. By leveraging multiple immune cell-specific multi-omics data across genomic, epigenetic, transcriptomic, proteomic and 3D chromatin interaction information, we devised an integrative analysis frame to dissect the functionality of noncoding GWAS SNPs (fnGWAS) associated with 19 autoimmune diseases.
This website collected multiple resources including:
1) All analysis results for 19 autoimmune diseases: functional scores on all noncoding autoimmune SNPs, allelic regulatory activities underlying functional SNPs (SNP2Function), regulatory target genes of functional SNPs (SNP2Gene), immunologically related functions for predicted target genes (Gene2Disease) as well as clinical drug applications for target genes (Gene2Drug).
2) Download link for precomputed functional scores for all autosomal noncoding SNPs from the 1000 genome European V3 data, annotated potential functional mechanisms that underlie allelic regulatory effect for whole genome SNPs, disease related functions as well as potential drug applications for whole genome genes.
3) Download link for packaged local pipeline for fnGWAS with user-definable input annotation data and parameters that could be run at any local Linux server.
Collectively, this website provided compressive unique resource linking noncoding GWAS SNPs to autoimmune disease pathogenesis, which may greatly facilitate the future experimental follow-up as well as clinical exploitation of drug repurposing.
Chen XF, Guo MR, Duan YY, Jiang F, Wu H, Dong SS, Zhou XR, Thynn HN, Liu CC, Zhang L, Guo Y, Yang TL. Multiomics dissection of molecular regulatory mechanisms underlying autoimmune-associated noncoding SNPs. JCI Insight. 2020;5(17):e136477.