Fine-mapping causal tissues and genes at disease-associated loci.

ABSTRACT: Complex diseases often have distinct mechanisms spanning multiple tissues. We propose tissue-gene fine-mapping (TGFM), which infers the posterior inclusion probability (PIP) for each gene-tissue pair to mediate a disease locus by analyzing summary statistics and expression quantitative trait loci (eQTL) data; TGFM also assigns PIPs to non-mediated variants. TGFM accounts for co-regulation across genes and tissues and models uncertainty in cis-predicted expression models, enabling correct calibration. We applied TGFM to 45 UK Biobank diseases or traits using eQTL data from 38 Genotype-Tissue Expression (GTEx) tissues. TGFM identified an average of 147 PIP > 0.5 causal genetic elements per disease or trait, of which 11% were gene-tissue pairs. Causal gene-tissue pairs identified by TGFM refl

SUBMITTER: Strober BJ 

PROVIDER: S-EPMC12413687 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature