Blood cell traits' GWAS loci colocalization with variation in PU.1 genomic occupancy prioritizes causal noncoding regulatory variants.

ABSTRACT: Genome-wide association studies (GWASs) have uncovered numerous trait-associated loci across the human genome, most of which are located in noncoding regions, making interpretation difficult. Moreover, causal variants are hard to statistically fine-map at many loci because of widespread linkage disequilibrium. To address this challenge, we present a strategy utilizing transcription factor (TF) binding quantitative trait loci (bQTLs) for colocalization analysis to identify trait associations likely mediated by TF occupancy variation and to pinpoint likely causal variants using motif scores. We applied this approach to PU.1 bQTLs in lymphoblastoid cell lines and blood cell trait GWAS data. Colocalization analysis revealed 69 blood cell trait GWAS loci putatively driven by PU.1 occupancy vari

SUBMITTER: Jeong R 

PROVIDER: S-EPMC10363807 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature