LINKED MARKERS AND AGE AT DIAGNOSIS

This paper examines the relationship between age at diagnosis and mark ers linked to a disease trait using 100 replicates from Problem 2A in Genetic Analysis Workshop 10. After establishing the relationship betw een age and the quantitative trait used to define affection status, Q1 , we evaluated the relationship between age at diagnosis and a marker which was linked with Q1. We found that the presence of an F allele at marker 15 on chromosome 5 was significantly associated with delayed a ge of diagnosis. When we evaluated 100 replicates, we found that the r egression coefficients in the survival analyses were separated into tw o approximately normal distributions. The location of these distributi ons was solely reflective of the presence of affected individuals with the F allele in a particular replicate. In the replicates in one of t he distributions, we found tremendous changes in the variance after em ploying survival models for dependent data. While we suggest that surv ival analysis of dependent data may be an important tool in investigat ing genotype specific alterations in age at event, the findings of thi s study indicate that the method used may be very sensitive to certain types of missing data. (C) 1997 Wiley-Liss, Inc.