SNP interaction pattern identifier (SIPI): an intensive search for SNP-SNP interaction patterns.
Date
2017-03-15Author
Lin, H-Y
Chen, D-T
Huang, P-Y
Liu, Y-H
Ochoa, A
Zabaleta, J
Mercante, DE
Fang, Z
Sellers, TA
Pow-Sang, JM
Cheng, C-H
Eeles, R
Easton, D
Kote-Jarai, Z
Amin Al Olama, A
Benlloch, S
Muir, K
Giles, GG
Wiklund, F
Gronberg, H
Haiman, CA
Schleutker, J
Nordestgaard, BG
Travis, RC
Hamdy, F
Pashayan, N
Khaw, K-T
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, Y-J
PRACTICAL Consortium,
Park, JY
Type
Journal Article
Metadata
Show full item recordAbstract
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. AVAILABILITY AND IMPLEMENTATION: The SIPI software is freely available at http://publichealth.lsuhsc.edu/LinSoftware/ . CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Collections
Subject
PRACTICAL Consortium
Humans
Prostatic Neoplasms
Genetic Predisposition to Disease
Epistasis, Genetic
Polymorphism, Single Nucleotide
Models, Genetic
Software
Male
Matrix Metalloproteinase 16
Statistics as Topic
Genetic Association Studies
ErbB Receptors
Research team
Oncogenetics
Language
eng
Date accepted
2016-11-28
License start date
2017-03
Citation
Bioinformatics (Oxford, England), 2017, 33 (6), pp. 822 - 833
Publisher
OXFORD UNIV PRESS