Nonparametric trend statistic incorporating dispersion differences in sib pair linkage for quantitative traits.

The Haseman-Elston (HE) regression method and its extensions are widely used in genetic studies for detecting linkage to quantitative trait loci (QTL) using sib pairs. The principle underlying the simple HE regression method is that the similarity in phenotypes between two siblings increases as they share an increasing number of alleles identical by descent (IBD) from their parents at a particular marker locus. In such a procedure, similarity was identified with the locations, that is, means of groups of sib pairs sharing 0, 1, and 2 alleles IBD. A more powerful, rank-based nonparametric test to detect increasing similarity in sib pairs is presented by combining univariate trend statistics not only of locations, but also of dispersions of the squared phenotypic differences of two siblings for three groups. This trend test does not rely on distributional assumptions, and is applicable to the skewed or leptokurtic phenotypic distributions, in addition to normal or near normal phenotypic distributions. The performances of nonparametric trend statistics, including nonparametric regression slope, are compared with the HE regression methods as genetic linkage strategies.