Mode of inheritance of hand osteoarthritis in ethnically homogeneous pedigrees

Human Biology, Dec 2002 by Livshits, Gregory, Kalichman, Leonid, Cohen, Zvi, Kobyliansky, Eugene

The present study's results showed no statistically significant interaction between sex and extent of OA, neither at baseline nor in the rate of OA development. Moreover, the contribution of the putative major gene to the total phenotypic variance of OA did not depend on the individual's gender. However, genotype-age interaction was statistically significant and based on the likelihood ratio test could not be disregarded in the analysis. Still, the variance decomposition analysis showed that the contribution of this interaction to the total extent of variance was numerically low (about 0.6%). The same was true with respect to the other familial correlations, assuming that they reflect common spouse and shared sibling environment.

The main factor influencing the extent of OA development was age, contributing some 72.8% to total variance (vs. 14.5% for a putative single gene), regardless of the individual's gender. This finding is in good agreement with the results of epidemiological research that indicated that more than 70% of both men and women suffer from hand OA by the age of 65 years (Buckwalter and Martin 1995). The contribution of the putative major gene on age- and sex-adjusted OA phenotype variation is 55% (Model 1) in the present study, a finding that is in good conformity with results received by other investigators (Spector et al. 1996; Chitnavis et al. 1997; Felson et al 1998). The significance of this finding is that although both our current study and that of Felson et al. (1998) suggest the existence of a single gene effect in the etiology of OA, this effect would appear to be less principal when a sample that is heterogeneous for age is under investigation.

Acknowledgments This study was supported by the National Science Foundation of Israel through Grant No. 544/00. It was performed in partial fulfillment of doctoral degree requirements for L. Kalichman. Esther Eshkol is thanked for editorial assistance.

Received 13 December 2001; revision received 17 August 2002.

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