ezQTL: A Web Platform for Interactive Visualization and Colocalization of QTLs and GWAS Loci

Abstract

Genome-wide association studies (GWAS) have identified thousands of genomic loci associated with complex diseases and traits, including cancer. The vast majority of common trait-associated variants identified via GWAS fall in non-coding regions of the genome, posing a challenge in elucidating the causal variants, genes, and mechanisms involved. Expression quantitative trait locus (eQTL) and other molecular QTL studies have been valuable resources in identifying candidate causal genes from GWAS loci through statistical colocalization methods. While QTL colocalization is becoming a standard analysis in post-GWAS investigation, an easy web tool for users to perform formal colocalization analyses with either user-provided or public GWAS and eQTL datasets has been lacking. Here, we present ezQTL, a web-based bioinformatic application to interactively visualize and analyze genetic association data such as GWAS loci and molecular QTLs under different linkage disequilibrium (LD) patterns (1000 Genomes Project, UK Biobank, or user-provided data). This application allows users to perform data quality control for variants matched between different datasets, LD visualization, and two-trait colocalization analyses using two state-of-the-art methodologies (eCAVIAR and HyPrColoc), including batch processing. ezQTL is a free and publicly available cross-platform web tool, which can be accessed online at https://analysistools.cancer.gov/ezqtl.

Keywords: Colocalization; Expression quantitative trait locus; Genome-wide association study; Linkage disequilibrium; Visualization.

Figure 1

The architecture of the ezQTL analysis platform The overall structure of the ezQTL analysis platform including the input data types, analysis modules, and major features is shown. QTL, quantitative trait locus; SNP, single nucleotide polymorphism; QC, quality control; LD, linkage disequilibrium; GWAS, genome-wide association study.

Figure 2

Example of an ezQTL colocalization analysis between GWAS loci and eQTLs in a melanoma GWAS locus A. Correlation plot of Z-scores between QTLs and GWAS loci from the Locus QC module for identification of potentially mismatched alleles. Variants marked by “×” are C/G or A/T SNPs. B. A dual LocusZoom plot with eQTL association on top and GWAS association at the bottom from Locus Alignment. The pink diamond in the LocusZoom plot indicates the most significant SNP among the eQTL association, and the red circle highlights the current LD reference SNP. The pop-up window after clicking each SNP shows association information, additional actions, and links. C. LD matrix visualization from Locus LD. The purple diamond and red dashed line indicate the reference SNP. D. Colocalization analysis by both eCAVIAR and HyPrColoc from Locus Colocalization. E. QTL boxplot between genotype of reference SNP and gene quantification from Locus Quantification. eQTL, expression quantitative trait locus.