mV2G: a multiomic atlas for tissue-specific variant-to-gene prioritization

Abstract

The multiomic Variant-to-Gene (mV2G, https://mv2g.hbliulab.org) is a comprehensive atlas that integrates diverse functional genomic evidence to prioritize tissue-specific variant-to-gene (V2G) associations. While genome-wide association studies (GWAS) have identified millions of associations between genetic variants and diseases, translating these findings into biological mechanisms remains challenging because >90% of variants reside in noncoding regions. Existing V2G resources provide complementary regulatory evidence but are fragmented and often lack tissue-specific interpretation. To address this challenge, we constructed the mV2G atlas by integrating 24 types of functional genomic evidence across 50 human tissues, including molecular quantitative trait loci, enhancer–gene predictions, three-dimensional chromatin interactions, and experimental validation. The atlas contains 188,634,118 evidence-supported V2G pairs involving 13,618,039 variants and 69,521 genes. We further developed a unified tissue-specific V2G prioritization framework and prioritized 1,530,420 high-confidence functional V2G pairs involving 1,131,316 unique variants, with 87% exhibiting tissue-specificity. The mV2G atlas provides searchable variant- and gene-centered interfaces, an interactive browser for visualizing variants, target genes, cis-regulatory elements, and chromatin states, as well as downloadable datasets. By integrating complementary regulatory evidence into a unified framework, mV2G provides an accessible resource for interpreting the functional and phenotypic impact of genomic variation in relevant tissues for human diseases. GRAPHICAL ABSTRACT