CONSILIENCE-GWAS: A Web Resource for Parsed Heritability & Polygenic Score Analysis of Human GWAS Using Heterogeneous Functional Genomics Data

MotivationAddiction-related GWASs are increasingly important in understanding risk for substance use and disorders (SUDs). GWASs have begun to identify loci associated with SUDs and other complex traits, but most associated loci necessitate functional evidence to translate and prioritize. Data depots of functional evidence in tissues, cell types, and experimental paradigms across organisms hold significant promise when integrated with GWAS. Model organisms can provide crucial evidence for gene roles in behaviors; however, public facing resources connecting these data types and allowing for a comprehensive assessment and integration of functional evidence are limited. We address this technological gap by introducing the CONSILIENCE-GWAS analytical webtool that simplifies the aggregation, analysis, and visualization of the enrichment of model organism functional data in human GWAS. ResultsWe developed CONSILIENCE-GWAS to investigate how GWAS results are enriched by functional evidence within and across model systems. CONSILIENCE-GWAS incorporates enrichment pipelines for LD Score Regression and gene-set based polygenic score creation using user-supplied GWAS results and genotype data. CONSILIENCE-GWAS integrates with GENEWEAVER-GWAS via APIs, allowing end-users to upload, curate, compare, analyze, and share their results. GENEWEAVER integration facilitates the efficient identification of enriched gene sets across species and improves the interpretation of non-coding variants in tissue-specific contexts. We demonstrate features of CONSILIENCE-GWAS using publicly available data from a published enrichment analysis of alcohol consumption in Mus musculus translated to human GWAS of alcohol use and disorder. Availability and ImplementationCONSILIENCE-GWAS is freely available on the web at https://consilience.bgalab.emory.edu.