A1 Refereed original research article in a scientific journal
SNP interaction pattern identifier (SIPI): an intensive search for SNP-SNP interaction patterns
Authors: Lin HY, Chen DT, Huang PY, Liu YH, Ochoa A, Zabaleta J, Mercante DE, Fang Z, Sellers TA, Pow-Sang JM, Cheng CH, Eeles R, Easton D, Kote-Jarai Z, Al Olama AA, Benlloch S, Muir K, Giles GG, Wiklund F, Gronberg H, Haiman CA, Schleutker J, Nordestgaard BG, Travis RC, Hamdy F, Pashayan N, Khaw KT, Stanford JL, Blot WJ, Thibodeau SN, Maier C, Kibel AS, Cybulski C, Cannon-Albright L, Brenner H, Kaneva R, Batra J, Teixeira MR, Pandha H, Lu YJ, Park JY
Publisher: OXFORD UNIV PRESS
Publication year: 2017
Journal: Bioinformatics
Journal name in source: BIOINFORMATICS
Journal acronym: BIOINFORMATICS
Volume: 33
Issue: 6
First page : 822
Last page: 833
Number of pages: 12
ISSN: 1367-4803
eISSN: 1460-2059
DOI: https://doi.org/10.1093/bioinformatics/btw762
Motivation: Testing SNP-SNP interactions is considered as a 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 meaningful interaction patterns for a binary outcome. SIPI takes non-hierarchical models, inheritance modes and mode coding direction into consideration. The simulation results show that SIPI has higher power than MDR (Multifactor Dimensionality Reduction), AA_Full,Geno_Full (full interaction model with additive or genotypic mode) and SNPassoc in detecting interactions. Applying SIPI to the prostate cancer PRACTICAL consortium data with approximately 21 000 patients, the four SNP pairs in EGFR-EGFR, EGFR-MMP16 and EGFR-CSF1 were found to be associated with prostate cancer aggressiveness with the exact or similar pattern in the discovery and validation sets. A similar match for external validation of SNP-SNP interaction studies is suggested. We demonstrated that SIPI not only searches for more meaningful interaction patterns but can also overcome the unstable nature of interaction patterns.
