title: eQTL epistasis: detecting epistatic effects and inferring hierarchical relationships of genes in biological pathways.
abstract: BACKGROUND
  Epistasis is the interactions among multiple genetic variants. It has emerged to explain the 'missing heritability' that a marginal genetic effect does not account for by genome-wide association studies, and also to understand the hierarchical relationships between genes in the genetic pathways. The Fisher's geometric model is common in detecting the epistatic effects. However, despite the substantial successes of many studies with the model, it often fails to discover the functional dependence between genes in an epistasis study, which is an important role in inferring hierarchical relationships of genes in the biological pathway.
  
  
  RESULTS
  We justify the imperfectness of Fisher's model in the simulation study and its application to the biological data. Then, we propose a novel generic epistasis model that provides a flexible solution for various biological putative epistatic models in practice. The proposed method enables one to efficiently characterize the functional dependence between genes. Moreover, we suggest a statistical strategy for determining a recessive or dominant link among epistatic expression quantitative trait locus to enable the ability to infer the hierarchical relationships. The proposed method is assessed by simulation experiments of various settings and is applied to human brain data regarding schizophrenia.
  
  
  METHODS
  The MATLAB source codes are publicly available at: http://biomecis.uta.edu/epistasis.
authors.affiliation: Department of Computer Science and Engineering, University of Texas at Arlington, Arlington, TX 76019, USA, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 66012, USA and Department of Mathematics, University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Mingon
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Computer Science and Engineering, University of Texas at Arlington, Arlington, TX 76019, USA, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 66012, USA and Department of Mathematics, University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Computer Science and Engineering, University of Texas at Arlington, Arlington, TX 76019, USA, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 66012, USA and Department of Mathematics, University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Hyung-Wook
authors.initials: HW
authors.lastname: Chun
authors.affiliation: Department of Computer Science and Engineering, University of Texas at Arlington, Arlington, TX 76019, USA, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 66012, USA and Department of Mathematics, University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Computer Science and Engineering, University of Texas at Arlington, Arlington, TX 76019, USA, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 66012, USA and Department of Mathematics, University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Computer Science and Engineering, University of Texas at Arlington, Arlington, TX 76019, USA, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 66012, USA and Department of Mathematics, University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Gao
mesh_terms: D001921:Brain / Q000502:physiology*; D003198:Computer Simulation; D004843:Epistasis, Genetic / Q000235:genetics*; D005796:Genes / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008957:Models, Genetic; D040641:Quantitative Trait Loci; D012559:Schizophrenia / Q000235:genetics*; D015398:Signal Transduction