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Affected kin‐pair IBD methods: Genetic models
Author(s) -
Motro Uzi,
Thomson Glenys,
Vogler G. P.
Publication year - 1991
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.1370080504
Subject(s) - haplotype , goodness of fit , inheritance (genetic algorithm) , linkage (software) , statistics , genetics , statistical hypothesis testing , genetic linkage , allele , mathematics , biology , gene
Cases of interest using affected sib‐pair methods to distinguish between recessive and additive (dominant) modes of inheritance of a disease‐predisposing gene involve goodness‐of‐fit tests with a small expected number in the “share‐zero parental haplotypes” category, as well as an unknown parameter, the frequency of the disease‐predisposing allele. Our simulations demonstrate that the real significance level of the chi‐square test using the three‐haplotype‐sharing IBD values (share 2, 1, and 0 parental haplotypes) is close to the assumed (.05) level in these cases, so that the haplotype‐sharing classes do not have to be lumped, which would leave no degrees of freedom for a statistical test. The validity of the chi‐square approximation in cases of small expected freqencies has previously been described, but the situations that have been considered do not cover the very small values in the share‐zero category that are often expected in the affected sib‐pair analysis, nor do they involve estimation of an unknown parameter. Although including IBD values from affected kin pairs other than sibs can be a very powerful tool in demonstrating linkage of a marker and disease, these pairs do not add power, in fact they reduce the power, of the chi‐square tests of goodness‐of‐fit of modes of inheritance.