Robust multipoint linkage analysis: an extension of the Haseman-Elston method
J.M. Olson
Genetic Epidemiology, 12(2),177-193 (1995)
Abstract
The use of multiple markers, rather than a single marker, can
increase the likelihood of detecting linkage to a locus underlying a
quantitative trait. In this paper, the Haseman-Elston sibpair method
is extended to include information from multiple markers. The result
is a linear regression of the squared pair trait difference on the
jointly estimated proportions of genes shared identical by descent
at the two closest flanking marker loci. The results strengthen the
theoretical motivation for the interval mapping technique proposed
by Fulker and Cardon [1994: Am J Hum Genet 54:1092-1103] and extend
the method to include information from multiple markers, account for
a trait dominance component, and examine the region just outside
that defined by the markers. Simulations show that modest increases
in power and substantial decreases in bias of parameter estimates
are obtained when identity-by-descent probabilities are jointly
estimated. The regression relationship is also developed for other
types of relative pairs.
Allele-sharing linkage analysis