Linkage analysis in heterogeneous and complex traits

Linkage analysis is generally carried out under single-gene models, while c omplex traits are thought to be under the control of multiple interacting g enes. Current issues related to linkage analysis for complex traits are dis cussed. It is argued that linkage analyses should be carried out for sub-ph enotypes, in addition to classical "affected-unaffected" phenotypes. Correl ations for phenotypes among family members are often computed on the basis of extreme phenotypes of a proband, which results in biased estimates. Meth ods for ascertainment corrections are recommended. A generalized version of heterogeneity analysis is introduced and are shown to provide an effective single-locus analysis for complex traits.