Affected kin‐pair IBD methods: Genetic models

Uzi Motro, Glenys Thomson*, G. P. Vogler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)317-327
Number of pages11
JournalGenetic Epidemiology
Volume8
Issue number5
DOIs
StatePublished - 1991

Keywords

  • disease parameter estimates
  • identity by descent
  • mode of inheritance

Fingerprint

Dive into the research topics of 'Affected kin‐pair IBD methods: Genetic models'. Together they form a unique fingerprint.

Cite this