FDHE-IW: A Fast Approach for Detecting High-Order Epistasis in Genome-Wide Case-Control Studies

Detecting high-order epistasis in genome-wide association studies (GWASs) is of importance when characterizing complex human diseases. However, the enormous numbers of possible single-nucleotide polymorphism (SNP) combinations and the diversity among diseases presents a significant computational challenge. Herein, a fast method for detecting high-order epistasis based on an interaction weight (FDHE-IW) method is evaluated in the detection of SNP combinations associated with disease. First, the symmetrical uncertainty (SU) value for each SNP is calculated. Then, the top-k SNPs are isolated as guiders to identify 2-way SNP combinations with significant interaction weight values. Next, a forward search is employed to detect high-order SNP combinations with significant interaction weight values as candidates. Finally, the findings were statistically evaluated using a G-test to isolate true positives. The developed algorithm was used to evaluate 12 simulated datasets and an age-related macular degeneration (AMD) dataset and was shown to perform robustly in the detection of some high-order disease-causing models.