title: A Bayesian model for detection of high-order interactions among genetic variants in genome-wide association studies.
abstract: BACKGROUND
  A central question for disease studies and crop improvements is how genetics variants drive phenotypes. Genome Wide Association Study (GWAS) provides a powerful tool for characterizing the genotype-phenotype relationships in complex traits and diseases. Epistasis (gene-gene interaction), including high-order interaction among more than two genes, often plays important roles in complex traits and diseases, but current GWAS analysis usually just focuses on additive effects of single nucleotide polymorphisms (SNPs). The lack of effective computational modelling of high-order functional interactions often leads to significant under-utilization of GWAS data.
  
  
  RESULTS
  We have developed a novel Bayesian computational method with a Markov Chain Monte Carlo (MCMC) search, and implemented the method as a Bayesian High-order Interaction Toolkit (BHIT) for detecting epistatic interactions among SNPs. BHIT first builds a Bayesian model on both continuous data and discrete data, which is capable of detecting high-order interactions in SNPs related to case--control or quantitative phenotypes. We also developed a pipeline that enables users to apply BHIT on different species in different use cases.
  
  
  CONCLUSIONS
  Using both simulation data and soybean nutritional seed composition studies on oil content and protein content, BHIT effectively detected some high-order interactions associated with phenotypes, and it outperformed a number of other available tools. BHIT is freely available for academic users at http://digbio.missouri.edu/BHIT/.
authors.affiliation: College of Computer Science and Technology, Jilin University, Changchun, Jilin, China. wangjue@missouri.edu.|Department of Computer Science, Informatics Institute, and Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA. wangjue@missouri.edu.
authors.forename: Juexin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Computer Science, Informatics Institute, and Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA. joshitr@missouri.edu.
authors.forename: Trupti
authors.initials: T
authors.lastname: Joshi
authors.affiliation: Division of Plant Sciences and National Center for Soybean Biotechnology (NCSB), University of Missouri, Columbia, MO, USA. valliyodanb@missouri.edu.
authors.forename: Babu
authors.initials: B
authors.lastname: Valliyodan
authors.affiliation: Division of Plant Sciences and National Center for Soybean Biotechnology (NCSB), University of Missouri, Columbia, MO, USA. shiha@missouri.edu.
authors.forename: Haiying
authors.initials: H
authors.lastname: Shi
authors.affiliation: College of Computer Science and Technology, Jilin University, Changchun, Jilin, China. ycliang@jlu.edu.cn.|Department of Computer Science, Informatics Institute, and Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA. ycliang@jlu.edu.cn.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Division of Plant Sciences and National Center for Soybean Biotechnology (NCSB), University of Missouri, Columbia, MO, USA. nguyenhenry@missouri.edu.
authors.forename: Henry T
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: Department of Statistics, Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA. jzhang47@gsu.edu.|Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA. jzhang47@gsu.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Computer Science and Technology, Jilin University, Changchun, Jilin, China. xudong@missouri.edu.|Department of Computer Science, Informatics Institute, and Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA. xudong@missouri.edu.
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D004843:Epistasis, Genetic; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D008390:Markov Chains; D008957:Models, Genetic; D009010:Monte Carlo Method; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D025941:Protein Interaction Mapping; D019655:Quantitative Trait, Heritable; D012984:Software; D013025:Glycine max / Q000235:genetics