The genetic influence on radiographic osteoarthritis is site specific at the hand, hip and knee

Abstract

Objective: To identify whether a shared genetic influence accounts for the occurrence of OA at different skeletal sites.

Methods: Multivariate modelling of data on prevalent radiographic OA at the hand (DIP, PIP and CMC joints), hip and knee joints assessed in 992 monozygotic and dizygotic female twin participants from the TwinsUK Registry.

Results: OA at all the five joint sites was heritable. Genetic influences were strongly correlated among joints in the hand; however, there was little evidence of common genetic pathways to account for the co-occurrence of OA at the hand, hip and knee.

Conclusions: While genetic influences are important in explaining the variation in occurrence of OA at the hand, hip and knee, there is no evidence that common or shared genetic factors determine the occurrence of disease across all these skeletal sites. The findings suggest that there are important aetiological differences in the disease that are site-specific in women. These results have implications for the design of studies examining the genetic basis of OA as well as for strategies aimed at preventing and treating the disease.

Fig. 1.

The multivariate models of the five OA sites. Models containing additive (A) genetic and unique environmental (E) components are depicted. The top panel illustrates the Cholesky model, the middle panel the independent pathway model and the lower panel the common pathway model. The Cholesky model contains 5 genetic factors (A₁–A₅) and five environmental factors (E₁–E₅) loading sequentially on the five OA phenotypes. The independent pathway model contains one common genetic factor (A_c) and one common environmental factor (E_c) shared by all five OA phenotypes, together with site-specific genetic and environmental components (labelled A and E). The common pathway model contains one shared underlying phenotype (P_c) itself determined by a genetic and environmental components (A_c and E_c), together with site-specific genetic and environmental components (labelled A and E).

Fig. 2.

Path coefficients of the common pathway model for all five OA variables. The figure shows parameter estimates for the path coefficients of the common pathway AE model, selected as the most appropriate depiction of the data. Thickness of the arrows represents the strength of the association. The squares of the path coefficients provide an estimate of the variance explained by common and specific genetic and environmental components.