A general test of association for complex diseases with variable age of onset.

Analysis of age of onset is a key factor in linkage and association studies of some complex genetic traits. Recent methodological developments are mainly concentrated on binary or quantitative traits, in which age of onset information is ignored. We propose a linkage disequilibrium-based Cox model and a robust score test for testing association between a marker and a disease with variable age of onset. The proposed model is semi-parametric, with an unspecified baseline hazard function. Simulation results indicate that the proposed methods have correct error rates and good statistical power, even in the presence of population admixture. This approach offers a solution to the problem of testing for marker associations when there is a variable age of onset.