The effect that genotyping errors have on the robustness of common linkage-disequilibrium measures

The rapid development of a dense single-nucleotide-polymorphism marker map has stimulated numerous studies attempting to characterize the magnitude an d distribution of background linkage disequilibrium (LD) within and between human populations. Although genotyping errors are an inherent problem in a ll LD studies, there have been few systematic investigations documenting th eir consequences on estimates of background LD. Therefore, we derived simpl e deterministic formulas to investigate the effect that genotyping errors h ave on four commonly used LD measures-D', r, Q, and d-in studies of backgro und LD. We have found that genotyping error rates as small as 3% can have s erious affects on these LD measures, depending on the allele frequencies an d the assumed error model. Furthermore, we compared the robustness of D', r , Q, and d, in the presence of genotyping errors. In general, Q and d are m ore robust than D' and r, although exceptions do exist. Finally, through st ochastic simulations, we illustrate how genotyping errors can lead to erron eous inferences when measures of LD between two samples are compared.