Leveraging large-scale biobanks for therapeutic target discovery.

ABSTRACT: Large biobanks, including the Million Veteran Program (MVP), the UK Biobank, and FinnGen, provide genetic association results for more than 1 million individuals for hundreds of phenotypes. To select targets for pharmaceutical development, as well as to improve the understanding of existing targets, we harmonized these studies and performed two-sample Mendelian randomization (MR) on 2,003 phenotypes using genetic variants associated with gene expression (derived from GTEx and eQTLGen) and plasma protein levels (derived from ARIC, Fenland, and deCODE) as proxies of target modulation. We found 69,669 gene-trait pairs with evidence (p ≤ 1.6 × 10^-9) for causal effects. From the selected gene-trait pairs, we observed 6,447 genes with strong causal evidence for at least one of 2,003 i

SUBMITTER: Ferolito BR 

PROVIDER: S-EPMC12799792 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature