Searching High-Order SNP Combinations for Complex Diseases Based on Energy Distribution Difference

Single nucleotide polymorphisms, a dominant type of genetic variants, have been used successfully to identify defective genes causing human single gene diseases. However, most common human diseases are complex diseases and caused by gene-gene and gene-environment interactions. Many SNP-SNP interaction analysis methods have been introduced but they are not powerful enough to discover interactions more than three SNPs. The paper proposes a novel method that analyzes all SNPs simultaneously. Different from existing methods, the method regards an individual's genotype data on a list of SNPs as a point with a unit of energy in a multi-dimensional space, and tries to find a new coordinate system where the energy distribution difference between cases and controls reaches the maximum. The method will find different multiple SNPs combinatorial patterns between cases and controls based on the new coordinate system. The experiment on simulated data shows that the method is efficient. The tests on the real data of age-related macular degeneration (AMD) disease show that it can find out more significant multi-SNP combinatorial patterns than existing methods.