Simple, Robust Linkage Tests for Affected Sibs

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 nonpar...

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Bibliographic Details
Published in:American journal of human genetics 1998-05, Vol.62 (5), p.1228-1242
Main Authors: Whittemore, Alice S., Tu, I-Ping
Format: Article
Language:English
Subjects:
Affected sib pairs
Affected sib triples
Automation
Biological and medical sciences
Constrained likelihood-ratio test
General aspects. Genetic counseling
Genetic Linkage
Humans
Means test
Medical genetics
Medical sciences
Models, Genetic
Models, Statistical
Nonparametric-linkage test
Statistical power
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Summary: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.
ISSN:0002-9297
1537-6605
DOI:10.1086/301820