Robust variance-components approach for assessing genetic linkage in pedigrees
C.I. Amos
American Journal of Human Genetics, 54(3),535-543 (Mar 1994)
Abstract
To assess evidence for genetic linkage from pedigrees, I developed a
limited variance-components approach. In this method, variability
among trait observations from individuals within pedigrees is
expressed in terms of fixed effects from covariates and effects due
to an unobservable trait-affecting major locus, random polygenic
effects, and residual nongenetic variance. The effect attributable
to a locus linked to a marker is a function of the additive and
dominance components of variance of the locus, the recombination
fraction, and the proportion of genes identical by descent at the
marker locus for each pair of sibs. For unlinked loci, the polygenic
variance component depends only on the relationship between the
relative pair. Parameters can be estimated by either
maximum-likelihood methods or quasi-likelihood methods. The forms of
quasi-likelihood estimators are provided. Hypothesis tests derived
from the maximum-likelihood approach are constructed by appeal to
asymptotic theory. A simulation study showed that the size of
likelihood-ratio tests was appropriate but that the monogenic
component of variance was generally underestimated by the likelihood
approach.
Allele-sharing linkage analysis