Nonparametric linkage regression. II: Identification of influential pedigrees in tests for linkage.

Abstract

We applied case-deletion-based diagnostics to the combined Caucasian genome scan data for asthma and IgE from the Collaborative Study on the Genetics of Asthma (CSGA) and German family studies in order to identify influential pedigrees in tests for linkage. These methods identified 12 pedigrees whose data appear not to fit the asthma linkage model and for whom alternative genetic and nongenetic explanations can be explored. The methods also identified four pedigrees for chromosome 1 and two pedigrees for chromosome 2 that provide strong evidence for linkage at their respective loci. Similarly, these methods helped identify four pedigrees that strongly influenced the linkage tests for IgE. From these data, we can construct an enriched subset of pedigrees to be used in further analysis for mapping region-specific putative trait predisposing loci.