TY - JOUR
T1 - Affected kin‐pair IBD methods
T2 - Genetic models
AU - Motro, Uzi
AU - Thomson, Glenys
AU - Vogler, G. P.
PY - 1991
Y1 - 1991
N2 - 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.
AB - 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.
KW - disease parameter estimates
KW - identity by descent
KW - mode of inheritance
UR - http://www.scopus.com/inward/record.url?scp=0026355570&partnerID=8YFLogxK
U2 - 10.1002/gepi.1370080504
DO - 10.1002/gepi.1370080504
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C2 - 1761204
AN - SCOPUS:0026355570
SN - 0741-0395
VL - 8
SP - 317
EP - 327
JO - Genetic Epidemiology
JF - Genetic Epidemiology
IS - 5
ER -