Linkage Disequilibrium Testing when Linkage Phase is Unknown

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Linkage disequilibrium, the nonrandom association of alleles from different loci, can provide valuable information on the structure of haplotypes in the human genome and is often the basis for evaluating the association of genomic variation with human traits among unrelated subjects. But, linkage phase of genetic markers measured on unrelated subjects is typically unknown, and so measurement of linkage disequilibrium, and testing whether it differs significantly from the null value of zero, requires statistical methods that can account for the ambiguity of unobserved haplotypes. A common method to test whether linkage disequilibrium differs significantly from zero is the likelihood-ratio statistic, which assumes Hardy-Weinberg equilibrium of the marker phenotype proportions. We show, by simulations, that this approach can be grossly biased, with either extremely conservative or liberal type I error rates. In contrast, we use simulations to show that a composite statistic, proposed by Weir and Cockerham, maintains the correct type I error rates, and, when comparisons are appropriate, has similar power as the likelihood-ratio statistic. We extend the composite statistic to allow for more than two alleles per locus, providing a global composite statistic, which is a strong competitor to the usual likelihood-ratio statistic.

Original languageEnglish (US)
Pages (from-to)505-512
Number of pages8
JournalGenetics
Volume166
Issue number1
DOIs
StatePublished - Jan 2004

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Linkage Disequilibrium
Haplotypes
Alleles
Human Genome
Genetic Markers
Phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Linkage Disequilibrium Testing when Linkage Phase is Unknown. / Schaid, Daniel J.

In: Genetics, Vol. 166, No. 1, 01.2004, p. 505-512.

Research output: Contribution to journalArticle

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