rs7775

A nested case-control study of 451 women with incident radiographic hip osteoarthritis (RHOA) and 601 controls from the Study of Osteoporotic Fractures found that FRZB rs288326 and rs7775 SNPs are associated with proximal femur shape (SSM Mode 2). Importantly, rs288326 showed a significant interaction with hip shape in predicting RHOA (p=0.022), with an odds ratio of 2.5 (95% CI 1.2-5.3) for the 4th quartile of Mode 2 in carriers of the variant allele.

Genome-wide association study identifying 14,938 osteoarthritis cases and approximately 39,000 controls found that the C-allele of rs3815148 on chromosome 7q22 (near GPR22 gene) is associated with 1.14-fold increased risk of knee/hand OA (p=8×10⁻⁸) and 30% increased risk for knee OA progression. The same study identified rs10248619 and rs6088813 with secondary associations to OA.

Large-scale meta-analysis of 14 collaborative studies examining associations between GDF5 rs143383, FRZB rs7775, and FRZB rs288326 polymorphisms with osteoarthritis (OA) of the hip, knee, and hand. GDF5 rs143383 showed strong association with knee OA (OR=1.15, P=9.4×10⁻⁷) with consistent effects across populations, but effects were heterogeneous for hip and hand OA. FRZB variants showed no significant overall effects on OA phenotypes.

A candidate gene association study of 6,752 women from the Study of Osteoporotic Fractures examined 31 polymorphisms in 18 candidate osteoporosis genes for associations with fracture risk and bone mineral density. ALOX15_G48924T (rs7220870) T/T genotype was associated with 33% higher hip fracture risk (HR=1.33, 95% CI 1.00-1.77); PRL_T228C (rs7739889) C alleles reduced nonvertebral fracture risk by ~20%; BMP2_A125611G (rs235764) G/G showed 51% higher vertebral fracture risk (OR=1.51, 95% CI 1.03-2.23); and MMP2_C595T (rs243865) T allele carriers had reduced vertebral fracture risk. No significant associations were found with total hip BMD.