title: iFORM/eQTL: an ultrahigh-dimensional platform for inferring the global genetic architecture of gene transcripts.
abstract: Knowledge about how changes in gene expression are encoded by expression quantitative trait loci (eQTLs) is a key to construct the genotype-phenotype map for complex traits or diseases. Traditional eQTL mapping is to associate one transcript with a single marker at a time, thereby limiting our inference about a complete picture of the genetic architecture of gene expression. Here, we implemented an ultrahigh-dimensional variable selection model to build a computing platform that can systematically scan main effects and interaction effects among all possible loci and identify a set of significant eQTLs modulating differentiation and function of gene expression. This platform, named iFORM/eQTL, was assembled by forward-selection-based procedures to tackle complex covariance structures of gene-gene interactions. iFORM/eQTL can particularly discern the role of cis-QTLs, trans-QTLs and their epistatic interactions in gene expression. Results from the reanalysis of a published genetic and genomic data set through iFORM/eQTL gain new discoveries on the genetic origin of gene expression differentiation in Caenorhabditis elegans, which could not be detected by a traditional one-locus/one-transcript analysis approach.
authors.affiliation: Department of Statistics, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Kirk
authors.initials: K
authors.lastname: Gosik
authors.affiliation: Department of Public Health Sciences Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Kong
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Rongling
authors.initials: R
authors.lastname: Wu
mesh_terms: D015870:Gene Expression; D020869:Gene Expression Profiling; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D014158:Transcription, Genetic
keywords: gene expression; eQTL; variable selection; genetic architecture