Linkage analysis of quantitative traits: increased power by using selected samples.

Although a number of methods have been developed for linkage analysis of quantitative traits, power is relatively poor unless there is a single major locus of very large effect. Here it is demonstrated that the use of selected samples (i.e., ascertainment of a proband with an extreme score on the quantitative measure) can dramatically increase power, especially when proband selection is performed on the tail of a distribution with an infrequent recessive gene. Depending on gene action and allele frequency, selected samples permit detection of a major locus that accounts for as little as 10%-20% of the phenotypic variation. The judicious use of selected samples can make an appreciable difference in the feasibility of linkage studies for quantitative traits.