Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium

Abstract

Objective To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. To investigate whether different OA definitions result in different association results, we created hip OA definitions used within the consortium in the Rotterdam Study-I and tested the association of hip OA with gender, age and BMI using one-way ANOVA. For radiographic OA, we standardized the hip, knee and hand ROA definitions and calculated prevalence's of ROA before and after standardization in 9 cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. Results In this consortium, all studies with symptomatic OA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee, hip and hand radiographic OA 5, 4 and 7 different definitions were used, respectively. Different hip OA definitions do lead to different association results. For example, we showed in the Rotterdam Study-I that hip OA defined as “at least definite JSN and one definite osteophyte” was not associated with gender (p=0.22), but defined as “at least one definite osteophyte” was significantly associated with gender (p=3×10−9). Therefore, a standardization process was undertaken for radiographic OA definitions. Before standardization a wide range of ROA prevalence's was observed in the 9 cohorts studied. After standardization the range in prevalence of knee and hip ROA was small. Standardization of SOA phenotypes was not possible due to the case-control design of the studies. Conclusion Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies.

Osteoarthritis and bone mineral density: are strong bones bad for joints?

“…As stated earlier, it is recognised that in any given patient with OA changes in different joint tissues (including cartilage, bone and synovium) may predominate. 84 Phenotyping OA, for example into hypertrophic versus atrophic variants based on the extent of bony change and osteophytosis visible radiographically, 24,85 attempts to identify these pathogenic subgroups. Many commentators now believe that the key to success in OA treatment may be rational targeting of treatments with a specific mode of action to patients with a relevant subtype of the disease.…”

Genome-wide association and functional studies identify theDOT1Lgene to be involved in cartilage thickness and hip osteoarthritis

“…These loci include a variant influencing expression of GDF5 (2, 3), a locus on chromosome 7q22 near the orphan receptor GPR22 (4,5), and a variant in MCF2L (6). The low number of identified loci can be explained by relatively low power caused by insufficient sample sizes and by phenotype heterogeneity, which is a well-known problem in epidemiology of OA (7). The diagnosis of OA is based on a combination of parameters, including both clinical features (pain and stiffness) and a structural damage score (the most widely used is the Kellgren and Lawrence score), which includes formation of new bone spurs (osteophyte formation) and reduction of the joint-space width (JSW), indicating cartilage degradation.…”

Finger Length Pattern as a Biomarker for Osteoarthritis and Chronic Joint Pain: A Population‐Based Study and Meta‐Analysis After Systematic Review

“…OA of the hip and the knee was scored by the Kellgren/Lawrence (K/L) grading system. The definition of having knee or hip OA was a K/L score of Ն2, as described previously (17). Total joint replacements (TJRs) due to primary OA visible on radiographs were considered as OA.…”

“…An overall grade for OA was scored by the K/L grading system. Hand OA was defined as having a K/L score Ն2 in 2 of 3 joint groups (DIP, PIP, and CMC1/TS), as previously described (17).…”