Disease-specific prioritization of non-coding GWAS variants based on chromatin accessibility

Non-protein-coding genetic variants are a major driver of the genetic risk for human disease; however, identifying which non-coding variants contribute to diseases and their mechanisms remains challenging. In-silico variant prioritization methods quantify a variant’s severity, but for most methods the specific phenotype and disease-context of the prediction remain poorly defined. For example, many commonly used methods provide a single, organism-wide score for each variant, while other methods summarize a variant’s impact in certain tissues and/or cell-types. Here we propose a complementary disease-specific variant prioritization scheme, which is motivated by the observation that variants contributing to disease often operate through specific biological mechanisms.