Joint tests of linkage and association for quantitative traits

In this paper we describe various study designs and analytic techniques for testing the joint hypothesis that a genetic marker is both linked to and associated with a quantitative phenotype. Issues of power and sampling are addressed. The distinction between methods that explicitly examine association and those that infer association by examining the distribution of allelic transmissions from a heterozygous parent is examined. Extensions to multivariate, multiallelic, and multilocus situations are addressed. Recent approaches that combine variance-components-based linkage analyses with joint tests of linkage in the presence of association for disentanglement of the linkage and association and the application of such methods to fine mapping are discussed. Finally, new classes of joint tests of linkage and association that do not require samples of related individuals are described. (C) 2001 Elsevier Science.