Adding power to Haseman and Elston’s (1972) method

Abstract

Haseman and Elston¹ proposed a model-free method for testing linkage between a polymorphic marker and a quantitative trait locus from data on a sample of independent sib pairs. In that method the squared sib-pair trait difference is regressed on the estimated proportion of alleles shared by the sibs at a marker locus, a negative regression coefficient suggesting linkage. It is possible to obtain more power by modelling the sib covariance, as in the variance component method of linkage analysis, and yet retain a method that is computationally fast, involving only linear regression. To do this it is only necessary to change the dependent variable from the squared trait difference to the difference between the squared mean-corrected sum and the squared trait difference. The method can accommodate sibships of arbitrary size by using generalized least squares and can be made more powerful by weighting the two components. The method is robust in large samples in the presence of any trait distribution, and, in the case of ascertained samples, the mean can be chosen to maximize power.