Sibling-based tests of linkage and association for quantitative traits

The transmission/disequilibrium test (TDT) developed by Spielman et al. can be a powerful family-based test of linkage and, in some cases, a test of a ssociation as well as linkage. It has recently been extended in several way s; these include allowance for implementation with quantitative traits, all owance for multiple alleles, and, in the case of dichotomous traits, allowa nce for testing in the absence of parental data. In this article, these thr ee extensions are combined, and two procedures are developed that offer val id joint tests of linkage and (in the case of certain sibling configuration s) association with quantitative traits, with use of data from siblings onl y, and that can accommodate biallelic or multiallelic loci. The first proce dure uses a mixed-effects (i.e., random and fixed effects) analysis of vari ance in which sibship is. the random factor, marker genotype is the red fac tor, and the continuous phenotype is the dependent variable. Covariates can easily be accommodated, and the procedure can be implemented in commonly a vailable statistical software. The second procedure is a permutation-based procedure. Selected power studies are conducted to illustrate the relative power of each test under a variety of circumstances.