A wider view of networks | Nature Reviews Genetics

Access through your institution Buy or subscribe At the heart of the new strategy is the ability to use transcriptional profiles as readouts of complex traits, capturing the interplay

between genetic variation and the environment. In the mouse study, Schadt and colleagues focused on a complex QTL region on chromosome 1 that had previously been associated with obesity. The

expression of many loci in this region correlates with metabolic traits such as weight and fat mass; the aim was then to construct co-expression networks and identify interconnected

sub-networks in liver and fat tissues in order to identify those components that respond, in _trans_, to the genetic perturbations in the complex QTL region. The statistical association

between several metabolic traits and changes in the co-expression network points to genes and connections that are causal to the trait itself. For example, in one of the sub-networks, which

was enriched for macrophage metabolic genes, expression traits were linked to every metabolic measurement tested, suggesting it mediates the changes across the traits. This statistically

based hypothesis was substantiated by identifying three genes — lipoprotein lipase (_Lpl_), lactamase β (_Lactb_) and protein phosphatase 1-like (_Ppm1l_) — as being truly casual; mutant

mice each showed metabolic and physiological properties of obesity. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution

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Contact customer support ORIGINAL RESEARCH PAPERS * Emilsson, V. et al. Genetics of gene expression and its effect on disease. _Nature_ 452, 423–428 (2008) Article  CAS  Google Scholar  *

Chen, Y. & Zhu, J. et al. Variations in DNA elucidate molecular networks that cause disease. _Nature_ 452, 429–435 (2008) Article  CAS  Google Scholar  Download references Authors *

Tanita Casci View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Casci,

T. A wider view of networks. _Nat Rev Genet_ 9, 321 (2008). https://doi.org/10.1038/nrg2367 Download citation * Issue Date: May 2008 * DOI: https://doi.org/10.1038/nrg2367 SHARE THIS ARTICLE

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