Abstract | ||
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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. |
Year | DOI | Venue |
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2011 | 10.1186/1756-0381-4-11 | BioData mining |
Keywords | Field | DocType |
multifactor dimensionality reduction,prediction model,confounding factor,linkage disequilibrium | Signal Sensitivity,Data mining,Confounding,Text mining,Linkage disequilibrium,Multifactor dimensionality reduction,Computer science,Software,Bioinformatics,SNP | Journal |
Volume | Issue | ISSN |
4 | 1 | 1756-0381 |
Citations | PageRank | References |
2 | 0.36 | 3 |
Authors | ||
3 |
Name | Order | Citations | PageRank |
---|---|---|---|
Benjamin J. Grady | 1 | 7 | 2.27 |
Eric Torstenson | 2 | 32 | 5.56 |
Marylyn D. Ritchie | 3 | 692 | 86.79 |