An evaluation of a novel estimator of linkage disequilibrium

The analysis of systems involving many loci is important in population and quantitativegenetics. An important problem is the study of linkage disequilibrium (LD), a conceptrelevant in genome-enabled prediction of quantitative traits and in exploration ofmarker–phenotype associations. This article introduces a new estimator of a LDparameter (ρ²) that is much easier to compute than a maximumlikelihood (or Bayesian) estimate of a tetra-choric correlation. We examined theconjecture that the sampling distribution of the estimator of ρ²could be less frequency dependent than that of the estimator ofr², a widely used metric for assessing LD. This was donevia an empirical evaluation of LD in 806 Holstein–Friesian cattle using 771single-nucleotide polymorphism (SNP) markers and of HapMap III data on 21 991 SNPs(chromosome 3) observed in 88 unrelated individuals from Tuscany. Also, 1600 haplotypesover a region of 1 Mb simulated under the coalescent were used to estimate LD usingthe two measures. Subsequently, a simulation study compared the new estimator with that ofr² using several scenarios of LD and allelic frequencies.From these studies, it is concluded that ρ² provides a usefulmetric for the study of LD as the distribution of its estimator is less frequencydependent than that of the standard estimator of r².