A systems genetic analysis of high density lipoprotein metabolism and network preservation across mouse models

Peter Langfelder, Lawrence W. Castellani, Zhiqiang Zhou, Eric Paul, Richard Davis, Eric E. Schadt, Aldons J. Lusis, Steve Horvath, Margarete Mehrabian

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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).

Original languageEnglish
Pages (from-to)435-447
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1821
Issue number3
DOIs
StatePublished - Mar 2012
Externally publishedYes

Keywords

  • Co-expression
  • Genetics
  • HDL
  • Network

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