The choice of null distributions for detecting gene-gene interactions in genome-wide association studies

摘要

BackgroundIn genome-wide association studies (GWAS), the number of single-nucleotide polymorphisms (SNPs) typically ranges between 500,000 and 1,000,000. Accordingly, detecting gene-gene interactions in GWAS is computationally challenging because it involves hundreds of billions of SNP pairs. Stage-wise strategies are often used to overcome the computational difficulty. In the first stage, fast screening methods (e.g. Tuning ReliefF) are applied to reduce the whole SNP set to a small subset. In the second stage, sophisticated modeling methods (e.g., multifactor-dimensionality reduction (MDR)) are applied to the subset of SNPs to identify interesting interaction models and the corresponding interaction patterns. In the third stage, the significance of the identified interaction patterns is evaluated by hypothesis testing.