Multipoint linkage analysis under heterogeneity: Incorporation of parametric and nonparametric approaches

Using a recently developed multipoint parametric method, which tests for li nkage in the presence of heterogeneity, we performed a genome-wide search f or linkage using the German asthma data. Both dominant and recessive models were assumed in this parametric approach. Identity-by-descent (IBD) sharin g for affected sibs was also calculated to help identify an appropriate gen etic model and localize the trait locus. The strongest evidence for linkage was on chromosome 6 (p-value=0.00006) under the dominant model with hetero geneity. Using both linkage and IBD sharing information for D6S422 (36.55 c M) on chromosome 6, we conducted exploratory analyses to locate additional trait loci that might explain the linkage heterogeneity. We found evidence of heterogeneity between D6S422 and D11S4111 based on a test of association (p-value = 0.0015). (C) 2001 Wiley-Liss, Inc.