Background/Aims: In genetic studies of complex disease a consideration for the investigator is detection of joint effects. The Multifactor Dimensionality Reduction (MDR) algorithm searches for these effects with an exhaustive approach. Previously unknown aspects of MDR performance were the power to detect interactive effects given large numbers of non-model loci or varying degrees of heterogeneity among multiple epistatic disease models. Methods: To address the performance with many non-model loci, datasets of 500 cases and 500 controls with 100 to 10,000 SNPs were simulated for two-locus models, and one hundred 500-case/500-control datasets with 100 and 500 SNPs were simulated for three-locus models. Multiple levels of locus heterogeneity were simulated in several sample sizes. Results: These results show MDR is robust to locus heterogeneity when the definition of power is not as conservative as in previous simulation studies where all model loci were required to be found by the method. The results also indicate that MDR performance is related more strongly to broad-sense heritability than sample size and is not greatly affected by non-model loci. Conclusions: A study in which a population with high heritability estimates is sampled predisposes the MDR study to success more than a larger ascertainment in a population with smaller estimates.
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