A Systems Genetic Analysis of High Density Lipoprotein Metabolism and Network Preservation across Mouse Models


Peter Langfelder1, Lawrence W. Castellani2, Zhiqiang Zhou2, Eric Paul2, Richard Davis2, Eric E. Schadt4, Aldons J. Lusis1,2,3, Steve Horvath1,5, Margarete Mehrabian2,


1Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles
2Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles
3Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles
4Pacific Biosciences, Menlo Park, CA 94025
5Department of Biostatistics, University of California, Los Angeles

Contact: Peter (dot) Langfelder (at) gmail (dot) com, mehrabi (dot) m (at) gmail (dot) com

Abstract

We report a systems genetics analysis of high density lipoproteins (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.


Data

Expression, clinical phenotype, and genotype data are all included in this zip bundle:

Supplementary methods: R code for statistical analysis

Here we provide R code we used for the statistical analysis of the data. All code is provided in annotated pdf documents. Code can be copy-pasted into an R session to reproduce our results.
  1. Expression data pre-processing and cleaning
  2. eQTL analysis
  3. QTL analysis for HDL and other traits
  4. Standard (a.k.a. marginal) analysis: associations of individual genes with HDL and other traits
  5. Gene co-expression network analysis
  6. Causal testing
  7. Analysis of module preservation in adipose
  8. Analysis of module preservation in other crosses
  9. Analysis of preservation of module significance in other crosses

Supplementary figures

Supplementary figures, including captions are provided in this document.

Supplementary tables

Our supplementary tables provide more detailed information and resources for additional research and analysis.