Simple, Robust Linkage Tests for
Affected Sibs
Alice S. Whittemore1 and I-Ping Tu2
1Department of Health Research and Policy, Stanford
University School of Medicine; and
2 Stanford University School of Medicine, Stanford
American Journal of Human Genetics,
62:1228-1242(May 1998)
Abstract
Parametric-linkage analysis applied to large
pedigrees with many affected individuals has helped in
the identification of highly penetrant genes; but, for
diseases lacking a clear Mendelian inheritance pattern or
caused by several genes of low to moderate
penetrance, a more robust strategy is nonparametric
analysis applied to small sets of affected relatives, such
as affected sib pairs. Here we show that the robustness
of affected-sib-pair tests is related to the shape of the
constraint set for the sibs' identity-by-descent (IBD)
probabilities. We also derive a set of constraints for the
IBD probabilities of affected sib triples and use common
features of the shapes of the two constraint sets to
introduce new nonparametric tests (called "minmax"
tests) that are more robust than those in current use.
Asymptotic-power computations support the
robustness of the proposed minmax tests.
Allele-sharing linkage analysis