title: Integrating genetic and network analysis to characterize genes related to mouse weight.
abstract: Systems biology approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. We use microarray and genetic marker data from an F2 mouse intercross to examine the large-scale organization of the gene co-expression network in liver, and annotate several gene modules in terms of 22 physiological traits. We identify chromosomal loci (referred to as module quantitative trait loci, mQTL) that perturb the modules and describe a novel approach that integrates network properties with genetic marker information to model gene/trait relationships. Specifically, using the mQTL and the intramodular connectivity of a body weight-related module, we describe which factors determine the relationship between gene expression profiles and weight. Our approach results in the identification of genetic targets that influence gene modules (pathways) that are related to the clinical phenotypes of interest.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Anatole
authors.initials: A
authors.lastname: Ghazalpour
authors.forename: Sudheer
authors.initials: S
authors.lastname: Doss
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Susanna
authors.initials: S
authors.lastname: Wang
authors.forename: Christopher
authors.initials: C
authors.lastname: Plaisier
authors.forename: Ruth
authors.initials: R
authors.lastname: Castellanos
authors.forename: Alec
authors.initials: A
authors.lastname: Brozell
authors.forename: Eric E
authors.initials: EE
authors.lastname: Schadt
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Drake
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D016000:Cluster Analysis; D003433:Crosses, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci