SNP interaction pattern identifier (SIPI): an intensive search for SNP-SNP interaction patterns.

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. 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. The SIPI software is freely available at http://publichealth.lsuhsc.edu/LinSoftware/ . hlin1@lsuhsc.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Citation

Hui-Yi Lin, Dung-Tsa Chen, Po-Yu Huang, Yung-Hsin Liu, Augusto Ochoa, Jovanny Zabaleta, Donald E Mercante, Zhide Fang, Thomas A Sellers, Julio M Pow-Sang, Chia-Ho Cheng, Rosalind Eeles, Doug Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham G Giles, Fredrik Wiklund, Henrik Gronberg, Christopher A Haiman, Johanna Schleutker, Børge G Nordestgaard, Ruth C Travis, Freddie Hamdy, Nora Pashayan, Kay-Tee Khaw, Janet L Stanford, William J Blot, Stephen N Thibodeau, Christiane Maier, Adam S Kibel, Cezary Cybulski, Lisa Cannon-Albright, Hermann Brenner, Radka Kaneva, Jyotsna Batra, Manuel R Teixeira, Hardev Pandha, Yong-Jie Lu, PRACTICAL Consortium, Jong Y Park. SNP interaction pattern identifier (SIPI): an intensive search for SNP-SNP interaction patterns. Bioinformatics (Oxford, England). 2017 Mar 15;33(6):822-833

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PMID: 28039167

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