Knee osteoarthritis (KOA) is a common degenerative joint disease primarily caused by cartilage damage. The exact mechanism of its pathogenesis remains unclear, but known risk factors include age, obesity, inflammation, trauma, and genetic factors. This study aimed to identify disease-associated genes related to KOA by conducting whole-genome sequencing on a high-incidence KOA family and performing preliminary validation in the general population.

Six members from a three-generation, 18-member high-incidence KOA family were recruited, including four with KOA and two without. Whole-genome sequencing was performed on these six family members, and single nucleotide polymorphisms (SNPs) were screened using three deleteriousness prediction models: SIFT4G_Pred, Polyphen2_HDIV_Pred, and Polyphen2_HVAR_Pred. Additionally, 49 individuals from the general population were recruited, including 27 KOA patients and 22 healthy controls. MassArray SNP genotyping was conducted on these 49 individuals.

Whole-genome sequencing on the high-incidence KOA family members, combined with the three deleteriousness prediction models, identified 33 SNPs potentially associated with KOA. Based on these 33 SNPs and an additional 54 SNPs retrieved from the literature, preliminary validation was performed in the general population. The results revealed four SNPs that may be associated with KOA: rs10843013, rs12119908, rs2075164, and rs7953280. Among these, rs10843013 and rs7953280 were previously reported in the literature.

This study demonstrates that the development and progression of KOA are closely related to SNPs. When certain SNPs cluster within a family, the probability of KOA occurrence significantly increases. Moreover, these SNP loci also play an important role in influencing KOA susceptibility in the general population.