Familial clustering of erosive hand osteoarthritis in a large statewide cohort

Nikolas H Kazmers 1, Huong D Meeks 2, Kendra A Novak 1, Zhe Yu 2, Gail L Fulde 3, Joy L Thomas 3, Tyler Barker 4 5, Michael J Jurynec 1

Affiliations

PMID: 32940959
DOI: 10.1002/art.41520

Abstract

Objectives: Erosive hand osteoarthritis (EOA) is a severe and rapidly progressing subset of hand osteoarthritis. Its etiology remains largely unknown, which has hindered development of successful treatments. Our goals were to test the hypothesis that EOA would demonstrate familial clustering in a large statewide population linked to genealogical records, and to determine the association of potential risk factors with EOA.

Methods: Patients diagnosed with EOA were identified by searching 4,741,840‬ unique medical records from a comprehensive statewide database, the Utah Population Database (UPDB). Affected individuals were 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 multivariate conditional logistic regression and logistic regression models.

Results: We 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.

Conclusions: Familial clustering of EOA observed in a statewide database indicates a potential genetic contribution to the etiology of the disease. Age, sex, diabetes, and obesity are risk factors for EOA. 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.

Keywords: Erosive hand osteoarthritis; genetics; osteoarthritis; osteoarthritis cohort; osteoarthritis risk factors.