An information-gain approach to detecting three-way epistatic interactions in genetic association studies
We present in this paper a new method for
estimating three-way epistatic interactions in genetic association studies.
Hu T, Chen Y, Kiralis JW, Collins RL, Wejse C, Sirugo G, Williams
SM, Moore JH. An information-gain approach to detecting three-way epistatic
interactions in genetic association studies. J Am Med Inform Assoc. 2013 Feb
BACKGROUND: Epistasis has been historically used to describe the phenomenon
that the effect of a given gene on a phenotype can be dependent on one or more
other genes, and is an essential element for understanding the association
between genetic and phenotypic variations. Quantifying epistasis of orders
higher than two is very challenging due to both the computational complexity of
enumerating all possible combinations in genome-wide data and the lack of efficient
and effective methodologies.
OBJECTIVES: In this study, we propose a fast, non-parametric, and model-free
measure for three-way epistasis.
METHODS: Such a measure is based on information gain, and is able to
separate all lower order effects from pure three-way epistasis.
RESULTS: Our method was verified on synthetic data and applied to real data
from a candidate-gene study of tuberculosis in a West African population. In
the tuberculosis data, we found a statistically significant pure three-way
epistatic interaction effect that was stronger than any lower-order
CONCLUSION: Our study provides a
methodological basis for detecting and characterizing high-order gene-gene
interactions in genetic association studies.