title: A systems genetic analysis of high density lipoprotein metabolism and network preservation across mouse models.
abstract: We report a systems genetic analysis of high density lipoprotein (HDL) levels in an F2 intercross between inbred strains CAST/EiJ and C57BL/6J. We previously showed that there are dramatic differences in HDL metabolism in a cross between these strains, and we now report co-expression network analysis of HDL that integrates global expression data from liver and adipose with relevant metabolic traits. Using data from a total of 293 F2 intercross mice, we constructed weighted gene co-expression networks and identified modules (subnetworks) associated with HDL and clinical traits. These were examined for genes implicated in HDL levels based on large human genome-wide associations studies (GWAS) and examined with respect to conservation between tissue and sexes in a total of 9 data sets. We identify genes that are consistently ranked high by association with HDL across the 9 data sets. We focus in particular on two genes, Wfdc2 and Hdac3, that are located in close proximity to HDL QTL peaks where causal testing indicates that they may affect HDL. Our results provide a rich resource for studies of complex metabolic interactions involving HDL. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at UCLA, Gonda (Goldschmied) Neuroscience and Genetics Research Center, 695 Charles E. Young Drive South, Box 708822, Los Angeles, CA 90095-7088, USA. peter.langfelder@gmail.com
authors.forename: Peter
authors.initials: P
authors.lastname: Langfelder
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Castellani
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Eric
authors.initials: E
authors.lastname: Paul
authors.forename: Richard
authors.initials: R
authors.lastname: Davis
authors.forename: Eric E
authors.initials: EE
authors.lastname: Schadt
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Margarete
authors.initials: M
authors.lastname: Mehrabian
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003433:Crosses, Genetic; D059305:Diet, High-Fat; D005260:Female; D053263:Gene Regulatory Networks; D006655:Histone Deacetylases / Q000235:genetics*; D006824:Hybridization, Genetic; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008126:Lod Score; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D040641:Quantitative Trait Loci; D059467:Transcriptome; D000081102:WAP Four-Disulfide Core Domain Protein 2; D000099186:Histone Deacetylase 3
chemical_list: D002784:Cholesterol; D006655:Histone Deacetylases; D008075:Lipoproteins, HDL; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; D000099186:Histone Deacetylase 3; C576287:Wfdc2 protein, mouse