Asymptotic properties of affected-sib-pair linkage analysis
P. Holmans
American Journal of Human Genetics, 52(2),362-374
(Feb 1993)
Abstract
The likelihood-ratio method for affected-sib-pair analysis,
introduced by Risch, is a powerful method for detecting linkage when
the marker is not perfectly polymorphic, as is often the case. The
power of this method can be improved by restricting maximization to
the set of possible haplotype-sharing probabilities--denoted the
"possible triangle" method. The asymptotic distributions of the
resulting distributions are derived, enabling test criteria to be
found for any required test size (i.e., the probability of falsely
detecting linkage when none exists) and enabling p values to be
assigned to results. The criteria were found to be approximately
constant when the PIC of the marker varies, making them applicable
to any marker. The asymptotic power approximations were used to
investigate the relative performance of pairs with typed parents,
relative to those without, by comparing the sample sizes necessary
for a given power. Under certain circumstances, typing the parents
proved to be inefficient, even when PIC was low.
Allele-sharing linkage analysis