Affected Kin-pair IBD Methods: Genetic Models
U. Motro and G. Thomson
Genetic Epidemiology, 8(5), 317-27 (1991)
Abstract
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
frequencies 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.
Allele-sharing linkage analysis