The additive effect of individual genes in predicting risk of knee osteoarthritis.

Abstract

Genetic factors are important determinants of osteoarthritis (OA) but most individual genetic associations appear relatively modest. We aimed to answer whether carrying several genetic variants associated with knee OA could result in a greater risk of OA. Genotypes for 36 single nucleotide polymorphisms (SNPs) in 17 candidate genes previously associated with OA were analysed in 298 men and 305 women diagnosed with knee OA who met American College of Rheumatology (ACR) criteria, and in 297 male and 299 female age- and ethnicity-matched controls. The S-sum statistic method was used to select SNPs that contributed to knee OA, separately for men and women, and the coefficients from a logistic regression were used to add the genotypes in a new genetic risk variable. The odds ratio for individuals in the top quartile of the "genetic risk" variable compared to those in the bottom quartile was found to be 8.68 (95% CI 5.20-14.49, p<2x10(-16)) for women and 5.06 (95% CI 3.10-8.27, p<1x10(-10)) for men. Our data suggest that the additive information from a number of genetic variants can predict a substantial proportion of risk of knee OA.