Linkage analysis in heterogeneous and complex traits

Linkage analysis is generally carried out under singlegene models, while complex traits are thought to be under the control of multiple interacting genes. Current issues related to linkage analysis for complex traits are discussed. It is argued that linkage analyses should be carried out for sub-phenotypes, in addition to classical “affected-unaffected” phenotypes. Correlations for phenotypes among family members are often computed on the basis of extreme phenotypes of a proband, which results in biased estimates. Methods 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.