Practical application of residuals from survival models in quantitative trait linkage analysis

A number of familial diseases have an age-of-onset component, which can be considered as a censored quantitative trait. However, few software resource s are available for the use of time-to-event endpoints in linkage analysis. The purpose of this analysis was to examine the use of martingale residual s from Cox survival models as quantitative traits for familial diseases wit h variable age at onset. We used these residuals as quantitative traits in variance components linkage scans for the 50 replicates of the general popu lation simulated data for chromosomes 6 and 7. The region on chromosome 6 c ontaining markers D06G034 and D06G035 demonstrated evidence for linkage, co nsistent with the underlying genetic model. This analysis demonstrates the applicability of using martingale residuals as a quantitative trait in link age analyses of diseases that depend on age of onset. (C) 2001 Wiley-Liss, Inc.