Robust Variance-Components Approach for Assessing
Genetic Linkage in Pedigrees.
Amos CI
Department of Epidemiology, University of Texas, M.D. Anderson Cancer Center,
Houston 77030.
American Journal of Human Genetics, 54(3):535-543 (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.
Variance component linkage analysis