Human Gene Set: CHEN_METABOLIC_SYNDROM_NETWORK

For the Mouse gene set with the same name, see CHEN_METABOLIC_SYNDROM_NETWORK

Standard name CHEN_METABOLIC_SYNDROM_NETWORK
Systematic name M1920
Brief description Genes forming the macrophage-enriched metabolic network (MEMN) claimed to have a causal relationship with the metabolic syndrom traits.
Full description or abstract Identifying variations in DNA that increase susceptibility to disease is one of the primary aims of genetic studies using a forward genetics approach. However, identification of disease-susceptibility genes by means of such studies provides limited functional information on how genes lead to disease. In fact, in most cases there is an absence of functional information altogether, preventing a definitive identification of the susceptibility gene or genes. Here we develop an alternative to the classic forward genetics approach for dissecting complex disease traits where, instead of identifying susceptibility genes directly affected by variations in DNA, we identify gene networks that are perturbed by susceptibility loci and that in turn lead to disease. Application of this method to liver and adipose gene expression data generated from a segregating mouse population results in the identification of a macrophage-enriched network supported as having a causal relationship with disease traits associated with metabolic syndrome. Three genes in this network, lipoprotein lipase (Lpl), lactamase beta (Lactb) and protein phosphatase 1-like (Ppm1l), are validated as previously unknown obesity genes, strengthening the association between this network and metabolic disease traits. Our analysis provides direct experimental support that complex traits such as obesity are emergent properties of molecular networks that are modulated by complex genetic loci and environmental factors.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18344982   Authors: Chen Y,Zhu J,Lum PY,Yang X,Pinto S,MacNeil DJ,Zhang C,Lamb J,Edwards S,Sieberts SK,Leonardson A,Castellini LW,Wang S,Champy MF,Zhang B,Emilsson V,Doss S,Ghazalpour A,Horvath S,Drake TA,Lusis AJ,Schadt EE
Exact source Table 3S
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Source species Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
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Version history 3.1: First introduced

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