Research on single nucleotide polymorphisms interaction detection from network perspective

PLoS One. 2015 Mar 12;10(3):e0119146. doi: 10.1371/journal.pone.0119146. eCollection 2015.

Abstract

Single Nucleotide Polymorphisms (SNPs) found in Genome-Wide Association Study (GWAS) mainly influence the susceptibility of complex diseases, but they still could not comprehensively explain the relationships between mutations and diseases. Interactions between SNPs are considered so important for deeply understanding of those relationships that several strategies have been proposed to explore such interactions. However, part of those methods perform poorly when marginal effects of disease loci are weak or absent, others may lack of considering high-order SNPs interactions, few methods have achieved the requirements in both performance and accuracy. Considering the above reasons, not only low-order, but also high-order SNP interactions as well as main-effect SNPs, should be taken into account in detection methods under an acceptable computational complexity. In this paper, a new pairwise (or low-order) interaction detection method IG (Interaction Gain) is introduced, in which disease models are not required and parallel computing is utilized. Furthermore, high-order SNP interactions were proposed to be detected by finding closely connected function modules of the network constructed from IG detection results. Tested by a wide range of simulated datasets and four WTCCC real datasets, the proposed methods accurately detected both low-order and high-order SNP interactions as well as disease-associated main-effect SNPS and it surpasses all competitors in performances. The research will advance complex diseases research by providing more reliable SNP interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computational Biology / methods*
  • Epistasis, Genetic
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Models, Genetic*
  • Polymorphism, Single Nucleotide*

Grants and funding

This work was supported by The National Natural Science Foundation of China (grants No.61373051 and No.61175023), the Science and Technology Development Program of Jilin Province (grant No.20140204004GX, No. 20140520072JH), Project of Science and Technology Innovation Platform of Computing and Software Science (985 Engineering), and The Key Laboratory for Symbol Computation and Knowledge Engineering of the National Education Ministry of China, The Fundamental Research Funds for the Central Universities, China (grant No. 14QNJJ030). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.