Familial clustering of erosive hand osteoarthritis in a large statewide cohort

ObjectivesErosive hand osteoarthritis (EOA) is a severe and rapidly progressing form of osteoarthritis. Its etiology remains largely unknown, which has hindered development of successful treatments. Our primary goal was to test the hypothesis that EOA would demonstrate familial clustering in a large statewide population linked to genealogical records, which would suggest a genetic contribution to the pathogenesis of this condition. Our secondary purpose was to determine the association of potential risk factors with EOA.MethodsPatients diagnosed with EOA were identified by searching medical records from a comprehensive statewide database, the Utah Population Database (UPDB). Affected individuals were then mapped to pedigrees to identify high-risk families with excess clustering of EOA as defined by a Familial Standardized Incidence Ratio (FSIR) of ≥ 2.0. The magnitude of familial risk of EOA in related individuals was calculated using Cox regression models. Association of potential EOA risk factors was analyzed using conditional logistic regression and logistic regression models.ResultsWe identified 703 affected individuals linked to 240 unrelated high-risk pedigrees with excess clustering of EOA (FSIR ≥ 2.0). The relative risk of developing EOA was significantly elevated in first-degree relatives. There was a significant association with the diagnosis of EOA and age, sex, diabetes, and obesity.ConclusionsFamilial clustering of EOA observed in a statewide database indicates a potential genetic contribution to the etiology of the disease. Identification of causal gene variants in these high-risk families may provide insight into the genes and pathways that contribute to EOA onset and progression.