This study aims to identify novel candidate effector genes for osteoarthritis (OA) by generating the first whole genome chromosome conformation analysis (Hi-C) map of primary OA chondrocytes. Primary chondrocytes from 8 OA patients were subjected to Hi-C analysis to link chromosomal structure with genomic sequence. The identified chromatin loops were combined with OA GWAS results and epigenomic data to identify variants involved in gene regulation via enhancer-promoter interactions. The study identified 345 genetic variants within chromatin loop anchors associated with 77 OA GWAS signals. Ten of these variants reside in enhancer regions of 10 newly described active enhancer-promoter loops, leading to the identification of two new candidate effector genes, SPRY4 and PAPPA, and further supporting the known role of SLC44A2 in OA. The study provides insights into the regulatory landscape of OA and identifies potential high-value drug targets.This study aims to identify novel candidate effector genes for osteoarthritis (OA) by generating the first whole genome chromosome conformation analysis (Hi-C) map of primary OA chondrocytes. Primary chondrocytes from 8 OA patients were subjected to Hi-C analysis to link chromosomal structure with genomic sequence. The identified chromatin loops were combined with OA GWAS results and epigenomic data to identify variants involved in gene regulation via enhancer-promoter interactions. The study identified 345 genetic variants within chromatin loop anchors associated with 77 OA GWAS signals. Ten of these variants reside in enhancer regions of 10 newly described active enhancer-promoter loops, leading to the identification of two new candidate effector genes, SPRY4 and PAPPA, and further supporting the known role of SLC44A2 in OA. The study provides insights into the regulatory landscape of OA and identifies potential high-value drug targets.