From genetic causality to druggable targets: A multiomics framework identifies ZSCAN16 in gout pathogenesis.

ABSTRACT: ObjectiveGout is a prevalent form of inflammatory arthritis in which many patients respond suboptimally to current therapies. Drug development is hampered by a lack of genetically validated targets, leading to high clinical trial attrition. This study aimed to systematically identify and prioritize novel, druggable targets for gout via a multilayered genetic and functional genomics approach.MethodsWe performed two-sample Mendelian randomization (MR) using cis-expression quantitative trait locus (cis-eQTL) data and dual independent gout genome-wide association study (GWAS) cohorts (openGWAS and FinnGen). The candidate genes were subjected to a rigorous validation pipeline including Bayesian colocalization, phenome-wide association studies (PheWASs) to assess pleiotropy and on-target safety,

SUBMITTER: Chen C 

PROVIDER: S-EPMC12696314 | biostudies-literature | 2025 Oct-Dec

REPOSITORIES: biostudies-literature