Some Properties of a Variance Components Model for Fine-Mapping Quantitative Trait Loci

Identifying etiological variants for multifactorial traits by allelic association holds promise when many markers are available in close proximity. However, evidence for or against association at any particular marker does not provide any direct information about the influence of causal variants or the frequency of the etiologic allele(s). Recently, a variance components model of linkage and association was developed for quantitative traits which is sufficiently flexible to provide some insights into these issues. We show that this combined linkage/association model provides an estimate of the additive genetic variance of a trait that is attributable to disequilibrium between the marker and QTL. We use this estimate to construct approximate boundaries of the minimum level of disequilibrium between an observed marker and unobserved QTL and to delimit the permissible range of allele frequencies at the QTL based on available data at nearby markers. This information may facilitate fine-mapping studies of complex traits that aim to localize QTLs by assessment of association with many markers in a candidate region of interest.