Exploring Positional Candidate Genes: Linkage Conditional on Measured Genotype

Variance component methods for linkage analysis of quantitative traits are now well established and have been applied with great success. Numerous QTLs influencing both normal variation between individuals and biomedically relevant quantitative risk factors have been localized in recent years. These findings have motivated recent methodological developments focused on the next step in the analytical process, moving beyond QTL localization by linkage to identifying specific genes and the functional polymorphisms in them that influence the phenotype of interest. In this paper, we describe one approach to exploring positional candidate genes in a region of linkage, linkage analysis conditional on measured genotype. We illustrate the properties of this method using simulated data from Genetic Analysis Workshops 10 and 12 and discuss example applications of this method to human quantitative trait data.