rs4836732

A GWAS meta-analysis of 15,934 individuals identified 9 SNPs across 8 loci associated with hip shape phenotypes derived from DXA scans. Five SNPs were associated with hip shape mode 1 (HSM1) at genome-wide significance (p < 5×10⁻⁹), three with HSM2, and one with HSM5. Most loci were close to genes involved in endochondral bone formation (SOX9, PTHLH, FGFR4, NKX3-2, DICER1, RUNX1, HHIP) and also associated with height. Three SNPs showed associations with hip osteoarthritis and one with hip fracture risk.

This genome-wide association study (GWAS) of radiographic tibiofemoral knee osteoarthritis in 3,898 cases and 3,168 controls from four North American cohorts identified one novel locus near LSP1P3 (rs4867568, OR=0.84, P=3.02×10⁻⁶) and confirmed associations with previously reported loci GDF5 (rs143383, OR=1.12, P=2.13×10⁻³) and FTO (rs8044769, OR=1.10, P=6.13×10⁻³). Despite the large sample size and standardized radiographic phenotyping, no variants achieved genome-wide significance, highlighting the polygenic nature of knee OA.

Candidate gene study of 4 SNPs in Russian population replicating GWAS-significant variants associated with stage 4 knee osteoarthritis. The A allele of rs6499244 in NFAT5 was identified as a risk factor for knee osteoarthritis in additive (OR=1.61, p=0.02) and recessive (OR=2.07, p=0.02) models. Functional analysis shows rs6499244 is located in DNase-hypersensitive regions and enhancers, associated with expression of 9 genes including NFAT5 itself.