Age of diagnosis-based linkage analysis in type 1 diabetes

Genetic linkage studies of type 1 diabetes have produced a number of conflicting results, suggesting a high degree of locus heterogeneity in this disease. Approaches which model such heterogeneity will increase the power to fine map susceptibility loci. Here, using data from a genome scan of 356 affected sib pairs with type 1 diabetes, we performed heterogeneity analysis based on similarity of age at diagnosis of the sib pairs. We observed linkage to the region on chromosome 4p16.3 in sib pairs both diagnosed over the age of 10 years, whilst there was no evidence for linkage in sib pairs diagnosed before age 10 years. In contrast the sib pairs diagnosed before the age of 10 years demonstrated linkage to IDDM10, on chromosome 10p. Age of diagnosis-based heterogeneity analyses in complex diseases may be particularly helpful in mapping some susceptibility loci.