GWAS SVatalog: a visualization tool to aid fine-mapping of GWAS loci with structural variations

Background: Genome-wide association studies (GWAS) have been successful in identifying single nucleotide polymorphisms (SNPs) associated with phenotypic traits. However, SNPs form an incomplete set of variation across the genome and since a large percentage of GWAS-significant SNPs lie in non-coding regions, their impact on a given trait is difficult to decipher. Recognizing whether these SNPs are tagging other polymorphisms, like structural variations (SV), is an important step towards understanding the putative causal variation at GWAS loci. Results: Here, we develop GWAS SVatalog (https://svatalog.research.sickkids.ca/), a novel open-source web tool that computes and visualizes linkage disequilibrium (LD) between SVs and GWAS-associated SNPs throughout the human genome. The tool combines GWAS Catalog′s SNP-trait association data across 14,479 phenotypes with LD statistics calculated between 35,732 SVs and 116,870 SNPs identified in 101 whole-genome long-read sequences. We use GWAS SVatalog to identify SVs that may explain GWAS loci for iron levels, refractive error, and Alzheimer′s disease, where previously SNPs were unable to provide a causal explanation. Conclusions: GWAS SVatalog advances the fine-mapping of GWAS loci with structural variations, enabling researchers to associate 35,732 common SVs with 14,479 phenotypes, accelerating the understanding of disease etiology.