biostudies-literatureUnknown16(1)Rahimov FInterleukin-1β (IL-1β) is dysregulated in chronic inflammatory diseases, yet the genetic factors influencing IL-1β production remain largely unknown. Myeloid-derived cells are the primary producers of IL-1β, which prompted a genome-wide CRISPR knockout screen in the human myeloid-derived U937 cells treated with lipopolysaccharide (LPS) to mimic inflammatory conditions and sorted for high and low intracellular IL-1β levels. A total of 295 genes are identified as regulators of IL-1β production, with 57 overlapping loci associated with inflammatory diseases, including the TNRC18 gene locus associated with multiple diseases in the Finnish population. U937 cells engineered with the Finnish-enriched rs748670681 risk allele demonstrate decreased expression of TNRC18 and an adjacent gene WIPI2, reNature communications10346https://www.ebi.ac.uk/biostudies/studies/S-EPMC12644769biostudies-literatureA genome-wide CRISPR screen identifies the TNRC18 gene locus as a regulator of inflammatory signaling.PMC12644769Shi Mden Hollander AIEspinoza CAWaring JFRahimov FWang JMahi NASchmidt MModi AAvram VAnton TVerduzco DSingh SKatlinski KVNyamugenda EMacoritto MTam JLu CChung NBiswas AStender JDGhosh SKeller AFlister MJPetiwala SfalseA genome-wide CRISPR screen identifies the TNRC18 gene locus as a regulator of inflammatory signaling.Interleukin-1β (IL-1β) is dysregulated in chronic inflammatory diseases, yet the genetic factors influencing IL-1β production remain largely unknown. Myeloid-derived cells are the primary producers of IL-1β, which prompted a genome-wide CRISPR knockout screen in the human myeloid-derived U937 cells treated with lipopolysaccharide (LPS) to mimic inflammatory conditions and sorted for high and low intracellular IL-1β levels. A total of 295 genes are identified as regulators of IL-1β production, with 57 overlapping loci associated with inflammatory diseases, including the TNRC18 gene locus associated with multiple diseases in the Finnish population. U937 cells engineered with the Finnish-enriched rs748670681 risk allele demonstrate decreased expression of TNRC18 and an adjacent gene WIPI2, re2025-01-01T00:00:00Z2025 Nov2026-06-05T18:52:20.829Z2026-05-20T03:14:14.058ZS-EPMC126447694128576710.1038/s41467-025-65277-y