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Novel measures of linkage disequilibrium that correct the bias due to population structure and relatedness

Abstract : Among the several linkage disequilibrium measures known to capture different features of the non-independence between alleles at different loci, the most commonly used for diallelic loci is the r(2) measure. In the present study, we tackled the problem of the bias of r(2) estimate, which results from the sample structure and/or the relatedness between genotyped individuals. We derived two novel linkage disequilibrium measures for diallelic loci that are both extensions of the usual r(2) measure. The first one, r(S)(2), uses the population structure matrix, which consists of information about the origins of each individual and the admixture proportions of each individual genome. The second one, r(V)(2), includes the kinship matrix into the calculation. These two corrections can be applied together in order to correct for both biases and are defined either on phased or unphased genotypes. We proved that these novel measures are linked to the power of association tests under the mixed linear model including structure and kinship corrections. We validated them on simulated data and applied them to real data sets collected on Vitis vinifera plants. Our results clearly showed the usefulness of the two corrected r(2) measures, which actually captured 'true' linkage disequilibrium unlike the usual r(2) measure.
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Submitted on : Thursday, February 4, 2016 - 8:20:51 PM
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Brigitte Mangin, Aurélie Siberchicot, S. Nicolas, Agnes Doligez, Patrice This, et al.. Novel measures of linkage disequilibrium that correct the bias due to population structure and relatedness. Heredity, Nature Publishing Group, 2012, 108 (3), pp.285-291. ⟨10.1038/hdy.2011.73⟩. ⟨hal-01267769⟩

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