TY - JOUR
T1 - The effect that genotyping errors have on the robustness of common linkage-disequilibrium measures
AU - Akey, Joshua M.
AU - Zhang, Kun
AU - Xiong, Momiao
AU - Doris, Peter
AU - Jin, Li
N1 - Funding Information:
We would like to thank Michael Akey and Anthony Berella for helpful discussions related to this work. M.X. was supported by National Institutes of Health grants GM56515 and E509912.
PY - 2001
Y1 - 2001
N2 - The rapid development of a dense single-nucleotide-polymorphism marker map has stimulated numerous studies attempting to characterize the magnitude and distribution of background linkage disequilibrium (LD) within and between human populations. Although genotyping errors are an inherent problem in all LD studies, there have been few systematic investigations documenting their consequences on estimates of background LD. Therefore, we derived simple deterministic formulas to investigate the effect that genotyping errors have on four commonly used LD measures - D′, r, Q, and d - in studies of background LD. We have found that genotyping error rates as small as 3% can have serious affects on these LD measures, depending on the allele frequencies and 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 more robust than D′ and r, although exceptions do exist. Finally, through stochastic simulations, we illustrate how genotyping errors can lead to erroneous inferences when measures of LD between two samples are compared.
AB - The rapid development of a dense single-nucleotide-polymorphism marker map has stimulated numerous studies attempting to characterize the magnitude and distribution of background linkage disequilibrium (LD) within and between human populations. Although genotyping errors are an inherent problem in all LD studies, there have been few systematic investigations documenting their consequences on estimates of background LD. Therefore, we derived simple deterministic formulas to investigate the effect that genotyping errors have on four commonly used LD measures - D′, r, Q, and d - in studies of background LD. We have found that genotyping error rates as small as 3% can have serious affects on these LD measures, depending on the allele frequencies and 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 more robust than D′ and r, although exceptions do exist. Finally, through stochastic simulations, we illustrate how genotyping errors can lead to erroneous inferences when measures of LD between two samples are compared.
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U2 - 10.1086/320607
DO - 10.1086/320607
M3 - Article
C2 - 11359212
AN - SCOPUS:0034981387
SN - 0002-9297
VL - 68
SP - 1447
EP - 1456
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
M1 - 61055
ER -