Pashayan, N; (2017) SNP Interaction Pattern Identifier (SIPI): An Intensive Search for SNP-SNP Interaction Patterns. Bioinformatics , 33 (6) pp. 822-833. 10.1093/bioinformatics/btw762.

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Abstract

Motivation: SNP-SNP interactions may be the key for overcoming bottlenecks of genetic association studies. However, related statistical methods for testing SNP-SNP interactions are underdeveloped. / Results: We propose the SNP Interaction Pattern Identifier (SIPI), which tests 45 biologically mean-ingful interaction patterns for a binary outcome. SIPI takes various inheritance modes and model structures (including non-hierarchical models) into consideration. The simulation results show that SIPI has higher power than MDR-LR (Multifactor Dimensionality Reduction-Logistic Regression), AA_Full, and SNPassoc in general. Applying SIPI to the prostate cancer PRACTICAL consortium data with approximately 21,000 patients, the two SNP pairs in EGFR-MMP16 and EGFR-EGFR were found to be associated with prostate cancer aggressiveness with the exact pattern in the discovery and validation sets. We demonstrated that SIPI not only searches for more meaningful interaction patterns but can also overcome the unstable nature of interaction patterns.

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