Integrative Proteome- and Phenome-Wide Assessment Uncovers Causal Protein Drivers and Drug Targets for Heterogeneous Kidney Diseases.

ABSTRACT: Interpreting proteomic associations with chronic kidney disease (CKD) is challenging due to the disease's clinical heterogeneity and complex overlap with systemic conditions. We present a framework that identifies causal circulating protein drivers of CKD and delineates their subtype-specific and systemic effects using electronic health record (EHR) data at biobank scale. Using proteome-wide Mendelian randomization, we instrumented cis-acting protein quantitative trait loci for 2,807 circulating proteins and tested them against detailed, EHR-based kidney function outcomes in 464,631 Million Veteran Program participants. Proteins were mapped to nine kidney disease subtypes defined by genome-wide association meta-analyses from the Million Veteran Program, UK Biobank, and FinnGen. Phenome-wid

SUBMITTER: Triozzi JL 

PROVIDER: S-EPMC12632676 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature