GWAS4D: multidimensional analysis of context-specific regulatory variant for human complex diseases and traits

Nucleic Acids Res. 2018 Jul 2;46(W1):W114-W120. doi: 10.1093/nar/gky407.

Abstract

Genome-wide association studies have generated over thousands of susceptibility loci for many human complex traits, and yet for most of these associations the true causal variants remain unknown. Tissue/cell type-specific prediction and prioritization of non-coding regulatory variants will facilitate the identification of causal variants and underlying pathogenic mechanisms for particular complex diseases and traits. By leveraging recent large-scale functional genomics/epigenomics data, we develop an intuitive web server, GWAS4D (http://mulinlab.tmu.edu.cn/gwas4d or http://mulinlab.org/gwas4d), that systematically evaluates GWAS signals and identifies context-specific regulatory variants. The updated web server includes six major features: (i) updates the regulatory variant prioritization method with our new algorithm; (ii) incorporates 127 tissue/cell type-specific epigenomes data; (iii) integrates motifs of 1480 transcriptional regulators from 13 public resources; (iv) uniformly processes Hi-C data and generates significant interactions at 5 kb resolution across 60 tissues/cell types; (v) adds comprehensive non-coding variant functional annotations; (vi) equips a highly interactive visualization function for SNP-target interaction. Using a GWAS fine-mapped set for 161 coronary artery disease risk loci, we demonstrate that GWAS4D is able to efficiently prioritize disease-causal regulatory variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology / trends
  • Genetic Diseases, Inborn*
  • Genome-Wide Association Study*
  • Genomics / methods
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • Quantitative Trait Loci / genetics*
  • Software*