Genome-Wide Association Study of Radiographic Knee Osteoarthritis in North American Caucasians

Objective: A major barrier to genetic studies of OA is the need to obtain large numbers of individuals with standardized radiographic evaluations for OA. To address this gap, we performed a genome-wide association study (GWAS) of radiographically-defined tibiofemoral knee OA in 3,898 cases and 3,168 controls from four well-characterized North American cohorts, and replication analysis of published OA loci. Methods: We performed meta-analysis using a two-stage design. Stage 1 (discovery) consisted of a GWAS meta-analysis of radiographic knee OA carried out in the Osteoarthritis Initiative and the Johnston County Osteoarthritis Project. Knee OA was defined as definitive osteophytes and possible joint space narrowing or total joint replacement in one or both knees. Stage 2 (validation) was performed in the Multicenter Osteoarthritis Study and Genetics of Osteoarthritis Study. We genotyped lead meta-analysis variants (P-value