The results did prove to be instructive about the localization of linkage peaks with respect to associated genes. Despite the presence of a strong, narrow linkage peak in our sample, none of the genes that passed permutation testing for significance were located with a 1 LOD—or 2 LOD—support interval for the primary, centromeric linkage peak with the AD with CD or SUI phenotype. Although simulations have previously demonstrated that the location of linkage peaks can vary substantially from the position of the underlying variant(s) [Roberts et al., 1999], the empirical results from this study clearly underscore the danger of focusing narrowly on follow-up of linkage regions as defined by the location of the peak. These findings appear to illustrate the hypothetical “worst case scenario” whereby clusters of associated genes are located on either side of the linkage peak, contributing to a peak location in the middle. Because linkage is a within-family test, whereas association is a between-family test, it is also possible that genetic heterogeneity between families could contribute to a detectable linkage signal for which association tests would not
