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The effects of linkage disequilibrium in large scale SNP datasets for MDR

BACKGROUND: In the analysis of large-scale genomic datasets, an important consideration is the power of analytical methods to identify accurate predictive models of disease. When trying to assess sensitivity from such analytical methods, a confounding factor up to this point has been the presence of...

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Autores principales: Grady, Benjamin J, Torstenson, Eric S, Ritchie, Marylyn D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108918/
https://www.ncbi.nlm.nih.gov/pubmed/21545716
http://dx.doi.org/10.1186/1756-0381-4-11
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author Grady, Benjamin J
Torstenson, Eric S
Ritchie, Marylyn D
author_facet Grady, Benjamin J
Torstenson, Eric S
Ritchie, Marylyn D
author_sort Grady, Benjamin J
collection PubMed
description BACKGROUND: In the analysis of large-scale genomic datasets, an important consideration is the power of analytical methods to identify accurate predictive models of disease. When trying to assess sensitivity from such analytical methods, a confounding factor up to this point has been the presence of linkage disequilibrium (LD). In this study, we examined the effect of LD on the sensitivity of the Multifactor Dimensionality Reduction (MDR) software package. RESULTS: Four relative amounts of LD were simulated in multiple one- and two-locus scenarios for which the position of the functional SNP(s) within LD blocks varied. Simulated data was analyzed with MDR to determine the sensitivity of the method in different contexts, where the sensitivity of the method was gauged as the number of times out of 100 that the method identifies the correct one- or two-locus model as the best overall model. As the amount of LD increases, the sensitivity of MDR to detect the correct functional SNP drops but the sensitivity to detect the disease signal and find an indirect association increases. CONCLUSIONS: Higher levels of LD begin to confound the MDR algorithm and lead to a drop in sensitivity with respect to the identification of a direct association; it does not, however, affect the ability to detect indirect association. Careful examination of the solution models generated by MDR reveals that MDR can identify loci in the correct LD block; though it is not always the functional SNP. As such, the results of MDR analysis in datasets with LD should be carefully examined to consider the underlying LD structure of the dataset.
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spelling pubmed-31089182011-06-07 The effects of linkage disequilibrium in large scale SNP datasets for MDR Grady, Benjamin J Torstenson, Eric S Ritchie, Marylyn D BioData Min Research BACKGROUND: In the analysis of large-scale genomic datasets, an important consideration is the power of analytical methods to identify accurate predictive models of disease. When trying to assess sensitivity from such analytical methods, a confounding factor up to this point has been the presence of linkage disequilibrium (LD). In this study, we examined the effect of LD on the sensitivity of the Multifactor Dimensionality Reduction (MDR) software package. RESULTS: Four relative amounts of LD were simulated in multiple one- and two-locus scenarios for which the position of the functional SNP(s) within LD blocks varied. Simulated data was analyzed with MDR to determine the sensitivity of the method in different contexts, where the sensitivity of the method was gauged as the number of times out of 100 that the method identifies the correct one- or two-locus model as the best overall model. As the amount of LD increases, the sensitivity of MDR to detect the correct functional SNP drops but the sensitivity to detect the disease signal and find an indirect association increases. CONCLUSIONS: Higher levels of LD begin to confound the MDR algorithm and lead to a drop in sensitivity with respect to the identification of a direct association; it does not, however, affect the ability to detect indirect association. Careful examination of the solution models generated by MDR reveals that MDR can identify loci in the correct LD block; though it is not always the functional SNP. As such, the results of MDR analysis in datasets with LD should be carefully examined to consider the underlying LD structure of the dataset. BioMed Central 2011-05-05 /pmc/articles/PMC3108918/ /pubmed/21545716 http://dx.doi.org/10.1186/1756-0381-4-11 Text en Copyright ©2011 Grady et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Grady, Benjamin J
Torstenson, Eric S
Ritchie, Marylyn D
The effects of linkage disequilibrium in large scale SNP datasets for MDR
title The effects of linkage disequilibrium in large scale SNP datasets for MDR
title_full The effects of linkage disequilibrium in large scale SNP datasets for MDR
title_fullStr The effects of linkage disequilibrium in large scale SNP datasets for MDR
title_full_unstemmed The effects of linkage disequilibrium in large scale SNP datasets for MDR
title_short The effects of linkage disequilibrium in large scale SNP datasets for MDR
title_sort effects of linkage disequilibrium in large scale snp datasets for mdr
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108918/
https://www.ncbi.nlm.nih.gov/pubmed/21545716
http://dx.doi.org/10.1186/1756-0381-4-11
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