Abstract

Abstract Unraveling the causal variants from genome wide association studies (GWASs) is pivotal for understanding genetic underpinnings of complex traits and diseases. Despite continuous efforts, tools to refine and prioritize GWAS signals need enhancement to address the direct causal implications of genetic variations. To overcome challenges related to statistical fine-mapping in identifying causal variants, CAUSALdb has been updated with novel features and comprehensive datasets, morphing into CAUSALdb2. This expanded repository integrates 15 057 updated GWAS summary statistics across 10 839 unique traits and implements both LD-based and LD-free fine-mapping approaches, including innovative applications of approximate Bayes Factor and SuSiE. Additionally, by incorporating larger LD reference panels such as TOPMED and UK Biobank, and integrating functional annotations via PolyFun, CAUSALdb2 enhances the accuracy and context of fine-mapping results. The database now supports interrogation of additional causal signals and offers sophisticated visualizations to aid researchers in deciphering complex genetic architectures. By facilitating a deeper and more precise characterisation of causal variants, CAUSALdb2 serves as a crucial tool for advancing the genetic analysis of complex diseases. Available freely, CAUSALdb2 continues to set benchmarks in the post-GWAS era, fostering the development of targeted diagnostics and therapeutics derived from responsible genetic research. Explore these advancements at http://mulinlab.org/causaldb.