• DOI:10.1038/ng1180
• Corpus ID: 13940856

PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes

@article{Mootha2003PGC1responsiveGI,
  title={PGC-1$\alpha$-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes},
  author={Vamsi K. Mootha and Cecilia M. Lindgren and K. -F. Eriksson and Aravind Subramanian and Smita Sihag and Joseph Leh{\'a}r and Pere Puigserver and Emma Carlsson and Martin Ridderstr{\aa}le and Esa Laurila and Nicholas E Houstis and Mark J. Daly and Nick J. Patterson and Jill P. Mesirov and Todd R. Golub and Pablo Tamayo and Bruce M Spiegelman and Eric S. Lander and Joel N. Hirschhorn and David M Altshuler and Leif C. Groop},
  journal={Nature Genetics},
  year={2003},
  volume={34},
  pages={267-273}
}

• V. Mootha, C. Lindgren, +18 authors L. Groop
• Published 1 July 2003
• Biology
• Nature Genetics

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-1α 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.