Score test for detecting linkage to quantitative traits.
The two most popular methods to detect linkage of a quantitative trait to a marker are the Haseman-Elston regression method and the variance components likelihood-ratio test. In the literature, these methods are frequently compared and the relative advantages and disadvantages of each method are well known. In this article, we derive a score test for the variance component attributable to a specific quantitative trait locus and show that for sib-pairs it is mathematically equivalent to a recently proposed version of the Haseman-Elston method that optimally combines the sum squared and the difference squared of the centered phenotype values of the sibs. Because score tests and likelihood-ratio tetsts are equivalent for large sample sizes, the variance components likelihood-ratio test is also asymptotically equivalent to this optimal Haseman-Elston test. This fact gives a theoretical explanation of the empirical observation from simulation studies reporting similar power of the variance components likelihood-ratio test and the optimal Haseman-Elston method. Perhaps more importantly for practical purposes, the score test can also be extended in a natural way to support the simultaneous analysis of more than two subjects and multivariate phenotypes.
Putter
H
H
Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands. h.putter@lumc.nl
Sandkuijl
L A
LA
van Houwelingen
J C
JC
D002874:Chromosome Mapping / Q000379:methods*; D008040:Genetic Linkage / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D009679:Nuclear Family; D019655:Quantitative Trait, Heritable