PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes - PubMed (original) (raw)
Cecilia M Lindgren, Karl-Fredrik Eriksson, Aravind Subramanian, Smita Sihag, Joseph Lehar, Pere Puigserver, Emma Carlsson, Martin Ridderstråle, Esa Laurila, Nicholas Houstis, Mark J Daly, Nick Patterson, Jill P Mesirov, Todd R Golub, Pablo Tamayo, Bruce Spiegelman, Eric S Lander, Joel N Hirschhorn, David Altshuler, Leif C Groop
Affiliations
- PMID: 12808457
- DOI: 10.1038/ng1180
PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
Vamsi K Mootha et al. Nat Genet. 2003 Jul.
Abstract
DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments.
Comment in
- PGC-1alpha at the crossroads of type 2 diabetes.
Attie AD, Kendziorski CM. Attie AD, et al. Nat Genet. 2003 Jul;34(3):244-5. doi: 10.1038/ng0703-244. Nat Genet. 2003. PMID: 12833045 No abstract available. - Statistical concerns about the GSEA procedure.
Damian D, Gorfine M. Damian D, et al. Nat Genet. 2004 Jul;36(7):663; author reply 663. doi: 10.1038/ng0704-663a. Nat Genet. 2004. PMID: 15226741 No abstract available.
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