Two-locus models of disease: comparison of likelihood and
nonparametric linkage methods
L.R. Goldin, D.E. Weeks
American Journal of Human Genetics, 53(4),908-915
(Oct 1993)
Abstract
The power to detect linkage for likelihood and nonparametric
(Haseman-Elston, affected-sib-pair, and affected-pedigree-member)
methods is compared for the case of a common, dichotomous trait
resulting from the segregation of two loci. Pedigree data for
several two-locus epistatic and heterogeneity models have been
simulated, with one of the loci linked to a marker locus. Replicate
samples of 20 three-generation pedigrees (16 individuals/pedigree)
were simulated and then ascertained for having at least 6 affected
individuals. The power of linkage detection calculated under the
correct two-locus model is only slightly higher than that under a
single locus model with reduced penetrance. As expected, the
nonparametric linkage methods have somewhat lower power than does
the lod-score method, the difference depending on the mode of
transmission of the linked locus. Thus, for many pedigree linkage
studies, the lod-score method will have the best power. However,
this conclusion depends on how many times the lod score will be
calculated for a given marker. The Haseman-Elston method would
likely be preferable to calculating lod scores under a large number
of genetic models (i.e., varying both the mode of transmission and
the penetrances), since such an analysis requires an increase in the
critical value of the lod criterion. The power of the
affected-pedigree-member method is lower than the other methods,
which can be shown to be largely due to the fact that marker
genotypes for unaffected individuals are not used.
Allele-sharing linkage analysis