Abstract
Analysis of epistasis, or gene–gene interactions, is of particular importance for revealing the molecular mechanisms of complex human diseases. Multiple genes, each of which has a moderate effect, might interact and produce a complex phenotypic trait. In this paper, we present a novel method of epistasis analysis, utilizing multiple phase-resolved haplotypes residing in different genomic regions. Prediction models can then be derived from the epistasis to indicate the susceptibility of a person to a dichrotomous phenotypic trait. The simulation results showed that the prediction accuracy of this method is dependent on the penetrance rate of the underlying model. The computation cost, on the other hand, is dependent on the number of genomic regions involved for the complex phenotypic trait.
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Appendix: Proof of Pr(R|X)Â +Â Pr(R C|X C)Â >Â 1
Appendix: Proof of Pr(R|X)Â +Â Pr(R C|X C)Â >Â 1
Making m a maker of a dichrotomous trait R, a sufficiently large relative risk of m against m C must be observed. That is
Since Pr(R) + Pr(R C) = 1, it can be derived that Pr(R|m C) = 1 − Pr(R C|mC);
Therefore
which will give
Hence, Pr(R|m) and Pr(R C|m C) cannot be smaller than 0.5 simultaneously.
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Liang, KH., Wu, YJ. Prediction of complex traits based on the epistasis of multiple haplotypes. J Hum Genet 52, 456–463 (2007). https://doi.org/10.1007/s10038-007-0140-7
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DOI: https://doi.org/10.1007/s10038-007-0140-7
