Osteoarthritis (OA) is the most common degenerative joint disorder in the elderlypopulation. To identify OA-associated genetic variants and candidate genes, we conducted a genome-wide association study (GWAS). A total 3,793 samples (476 cases wrist + knee and 3317 controls) from a community-based epidemiological study were genotyped using the Affymetrix SNP 5.0. An intronic SNP (rs4789934) in the TIMP2 (tissue inhibitor of metalloproteinase-2) showed the most significance with OA (odd ratio [OR] = 2.06, 95% confidence interval [CI] = 1.52-2.81, p = 4.01 x 10(-6)). Furthermore, a polymorphism (rs1352677) in the NKAIN2 (Na+/K+ transporting ATPase interacting 2) was suggestively associated with OA (OR = 1.43, CI = 1.22-1.66, p = 7.01 x 10(-6)). The present study provides new insights into the identification of genetic predisposing factors for OA.