ArticleTheoretical population biology2008
Mathematical properties of the r2 measure of linkage disequilibrium.
Article in Theoretical population biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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100 citing papers in PubMed.
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Abstract
Statistics for linkage disequilibrium (LD), the non-random association of alleles at two loci, depend on the frequencies of the alleles at the loci under consideration. Here, we examine the r(2) measure of LD and its mathematical relationship to allele frequencies, quantifying the constraints on its maximum value. Assuming independent uniform distributions for the allele frequencies of two biallelic loci, we find that the mean maximum value of r(2) is approximately 0.43051, and that r(2) can exceed a threshold of 4/5 in only approximately 14.232% of the allele frequency space. If one locus is assumed to have known allele frequencies--the situation in an association study in which LD between a known marker locus and an unknown trait locus is of interest--we find that the mean maximum value of r(2) is greatest when the known locus has a minor allele frequency of approximately 0.30131. We find that in 1/4 of the space of allowed values of minor allele frequencies and haplotype frequencies at a pair of loci, the unconstrained maximum r(2) allowing for the possibility of recombination between the loci exceeds the constrained maximum assuming that no recombination has occurred. Finally, we use r(max)(2) to examine the connection between r(2) and the D(') measure of linkage disequilibrium, finding that r(2)/r(max)(2)=D('2) for approximately 72.683% of the space of allowed values of (p(a),p(b),p(ab)). Our results concerning the properties of r(2) have the potential to inform the interpretation of unusual LD behavior and to assist in the design of LD-based association-mapping studies.
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