Haseman and Elston revisited

Haseman and Elston (H-E) [1972] proposed a method to detect quantitative tr ait loci by linkage to a marker. The squared sib-pair trait difference is r egressed on the proportion of marker alleles the pair is estimated to share identical by descent: a significantly negative regression coefficient sugg ests linkage. It has been shown that a maximum likelihood method that direc tly models the sib-pair covariance has more power. This increase in power c an also be obtained using the HE regression procedure by changing the depen dent variable from the squared difference to the mean-corrected product of the sibs' trait values. Multiple sibs in a sibship can be accommodated by a llowing for the correlations between pairs of products in a generalized lea st squares procedure. Multiple trait loci, including epistatic interactions , involve only multiple linear regression. Multivariate traits can use the method of Amos et al. [1990] to find the linear function of the traits that maximizes the evidence for linkage, which now leads more simply to a test of significance. Multiple markers can be the basis of a multipoint analysis . Results of simulation studies for a continuous trait are presented that i nvestigate Type I error and power. A similar general scheme can be used to study affected sib pairs, testing whether their identity by descent sharing probabilities are greater than would be expected in the absence of linkage , and to study other types of relative pairs. Genet. Epidemiol. 19:1-17, 20 00. (C) 2000 Wiley-Liss. Inc.