Genetic determinants of monocyte splicing are enriched for disease susceptibility loci.

ABSTRACT: Insights into variation in monocyte context-specific splicing and transcript usage are limited. Here, we perform paired gene and transcript QTL mapping across distinct immune states using RNA sequencing data of monocytes isolated from a cohort of 185 healthy Europeans incubated alone or in the presence of interferon gamma (IFN-γ) or lipopolysaccharide (LPS). We identify regulatory variants for 5749 genes and 8727 transcripts, with 291 context-specific transcript QTL colocalizing with GWAS loci. Notable disease relevant associations include IFN-γ specific transcript QTL at COVID-19 severity locus rs10735079, where allelic variation modulates context-specific splicing of OAS1, and at rs4072037, a risk allele for gastro-esophageal cancer, which associates with context-specific splicing of MUC

SUBMITTER: Nassiri I 

PROVIDER: S-EPMC12480492 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature