AbstractThousands of genetic loci have been identified as associated with hematological indices (red blood cell, white blood cell, and platelet related traits), as well as other complex traits and disease. However, most loci identified are noncoding and not clearly linked to target genes, and tools are needed to prioritize the most likely functional variants for experimental follow-up. We here describe VAMPIRE: Variant Annotation Method Pointing to Interesting Regulatory Effects, an interactive web application implemented in R Shiny (http://shiny.bios.unc.edu/vampire/) for blood cell trait associated loci from recent large multi-ethnic genome-wide association studies (GWAS). This tool efficiently displays information from blood cell relevant tissues on epigenomic signatures, functional and conservation summary scores, variant impact on protein and gene expression, chromatin conformation information from Hi-C and similar technologies, as well as publicly available GWAS and phenome-wide association study (PheWAS) results. Variants are classified into multiple prioritization categories according to these functional signatures. Leveraging data generated from independent functional validation experiments, we demonstrate that our prioritized variants are enriched within experimentally validated variant sets. VAMPIRE allows rapid prioritization and interpretation of blood cell trait GWAS variants and could be easily adapted for use with other complex trait GWAS results and extended to new annotation sources.Author SummaryMany large genome-wide association studies (GWAS) have recently been performed for blood cell traits, with thousands of associations identified. However, most of the associated variants are in noncoding regions and are often hard to interpret, link to genes, and prioritize for functional follow-up. Similar challenges exist for genetic studies of many other traits and diseases. Trying to translate knowledge of GWAS significant variants to target genes and biological insights, we here describe VAMPIRE: Variant Annotation Method Pointing to Interesting Regulatory Effects, an interactive web application implemented in R Shiny (http://shiny.bios.unc.edu/vampire/) for blood cell trait associated loci from recent large multi-ethnic GWAS. This tool displays a variety of information including epigenomic signatures, variant impact on protein and gene expression, chromatin conformation information, and publicly available GWAS and phenome-wide association study (PheWAS) results for other traits. We classified variants into annotation categories using this information, and show that variants in the highest priority categories are enriched in likely causal variant sets from previous functional experiments. We anticipate this tool will guide appropriate variants to prioritize for experimental validation for researchers studying blood cell traits, as well as providing an easily adaptable model for the creation of similar annotation tools for other complex traits and diseases.