LINKAGE STRATEGIES FOR GENETICALLY COMPLEX TRAITS .1. MULTILOCUS MODELS

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  • 1 February 1990
    • journal article
    • research article
    • Vol. 46  (2) , 222-228
Abstract
In order to investigate linkage detection strategies for genetically complex traits, multilocus models of inheritance need to be specified. Here, two types of multilocus model are described: (1) a multiplicative model, representing epistasis (interaction) among loci, and (2) an additive model, which is closely approximate genetic heterogeneity, which is characterized by no interlocus interaction. A ratio .lambda.R of risk for type R relatives that is compared with population prevalence is defined. For a single-locus model, .lambda.R - 1 decreases by a factor or two with each degree of relationship. The same holds true for an additive multilocus model. For a multiplicative (epistasis) model, .lambda.R - 1 decreases more rapidly than by a factor of two with degree of relationship. Examination of .lambda.R values for various classes of relatives can potentially suggest the presence of multiple loci and epistasis. For example, data for schizophrenia suggest multiple loci in interaction. It is shown in the second paper of this series that .lambda.R is the critical parameter in determining power to detect linkage by using affected relative pairs.