Background/Purpose: Osteoarthritis (OA) may affect multiple joint sites, including the hands, knees, and spine. Studies have suggested high heritability for hand OA, but OA in the major diarthrodial joint affected in the back, the facet joint, is unknown. Also, the heritability of OA has been found to be joint specific especially for hand and knee OA, but it is unknown whether facet joint OA shares heritability or even occurrence with OA elsewhere. Our goals were to determine whether there are shared genetic and environmental components to OA across distinct joint sites; we determined the heritabilities, genetic correlations, and environmental correlations between hand, knee, and facet joint OA.

Methods: Analyses were based on the Framingham Study, a community-based study in the US in which subjects were studied irrespective of OA status. We created a summary index score for hand OA by summing bilateral Kellgren-Lawrence (KL) scores at the 2^nd-5^th distal interphalangeal, 2^nd-5^th proximal interphalangeal, 1^st-5^thmetacarpophalangeal, thumb interphalangeal, and 1st carpometacarpal joints from posteroanterior hand radiographs. We assessed knee OA by summing KL scores from bilateral anteroposterior knee radiographs. We obtained measures of facet joint OA from thoracic CT imaging and summed Pathria and Weishaupt semi-quantitative scores at bilateral facet joints from T4 to L4 to obtain a summary index score. There were 1,259 individuals from the second generation cohort that underwent both hand and knee OA assessments. A total of 1,191 individuals from the second and third generation cohorts underwent facet joint OA assessments, of which 500 also had knee and hand OA assessments. We used a variance components method based on familial pedigrees to estimate heritability of hand, knee, and facet joint OA and bivariate models to estimate genetic and environmental correlations between OA at each joint site. All models were adjusted for age and sex.

Results: Mean age was 69±8 years and mean BMI was 29±5 kg/m². About 54% were women. Mean summary index score for hand, knee, and facet joint OA was 7±12 (range=0 to 69), 1±2 (range=0 to 8), and 28±13 (range=3 to 66), respectively. There were 266 families, ranging in size from 1 to 30 individuals. Estimated heritabilities for hand, knee, and facet joint OA were 62±9%, 13±9%, and 62±8%, respectively. Phenotypic correlation was significant between hand OA and knee OA (ρ_P(SE)=0.20 (0.03), p<0.01), but not between hand OA and facet joint OA (ρ_P(SE)=0.05), p=0.52). Neither genetic correlation (ρ_G(SE)=0.27 (0.24), p-0.28) nor environmental correlation (ρ_E(SE)=0.22 (0.11), p=0.07) was significant between hand and knee OA. For knee OA and facet joint OA, phenotypic correlation was significant (ρ_P(SE)=0.09 (0.04), p=0.04), but neither genetic (ρ_G(SE)=-0.12 (2.27), p=0.94), nor environmental correlation (ρ_E(SE)=0.19 (0.20), p=0.29), was significant.

Conclusion: Heritability was high (>60%) for OA at the hands and facet joints, and low (<15%) for OA at the knees. While knee OA commonly occurs with hand and facet joint OA, we found little evidence of genetic or environmental correlation across joint sites, suggesting that the genetic and environmental influences on OA are site-specific.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/genetic-and-environmental-correlation-of-osteoarthritis-at-the-hands-knees-and-spine/