A systems genetic analysis of high density lipoprotein metabolism and network
preservation across mouse models.
Authors Langfelder P, Castellani LW, Zhou Z, Paul E, Davis R, Schadt EE, Lusis AJ,
Horvath S, Mehrabian M
Submitted By Submitted Externally on 3/4/2015
Status Published
Journal Biochimica et biophysica acta
Year 2012
Date Published 3/1/2012
Volume : Pages 1821 : 435 - 447
PubMed Reference 21807117
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).

Investigators with authorship
Richard DavisUniversity of California Los Angeles