Epistasis in Quantitative Trait Locus Linkage Analysis: Interaction or Main Effect?

Abstract

This paper explores a two-locus variance components model of quantitative trait locus (QTL) linkage for sib-pairs that incorporates epistasis. For a range of epistatic models the expected variance components and noncentrality parameter per sib-pair can be calculated, to indicate the power to detect epistasis. In QTL linkage analysis, additive and epistatic effects are in fact partially confounded; as a result, variance components under incorrect submodels can be distorted, with two main implications. First, the analysis of a single locus can in fact detect a QTL that has no main effect but interacts epistatically with another (unmeasured) locus. That is, single-locus approaches do not necessarily preclude the detection of purely epistatically interacting loci. Second, because the nonepistatic variance component estimates in submodels can partially absorb epistatic variance when it is not explicitly modeled, power to formally detect epistasis is low.