Prioritization of candidate disease genes for metabolic syndrome by computational analysis of its defining phenotypes.

There is a rapid increase in the world-wide burden of disease attributed to metabolic syndrome, as defined by co-occurrence of an array of phenotypes including abdominal obesity, dysglycemia, hypertriglyceridemia, low levels of high density lipoprotein cholesterol, and hypertension. Familial studies clearly indicate a genetic component to the disease and many linkage studies have identified a large number of linked loci. No disease-causing genes, however, have been conclusively identified, most likely because this is a multigenic disease for which effects of many causative genes may be small and combined with environmental effects. To assist empirical identification of metabolic syndrome associated genes, we present here a novel computational approach to prioritize candidate genes. We have used linkage studies and the clinical and population-specific presentation of the disease to select a final candidate gene list of 19 most likely disease-causing genes. These are predominantly involved in chylomicron processing, transmembrane receptor activity, and signal transduction pathways. We propose here that information about the clinical presentation of a complex trait can be used to effectively inform computational prioritization of disease-causing genes for that trait.

Citation

Nicki Tiffin, Ikechi Okpechi, Carolina Perez-Iratxeta, Miguel A Andrade-Navarro, Rajkumar Ramesar. Prioritization of candidate disease genes for metabolic syndrome by computational analysis of its defining phenotypes. Physiological genomics. 2008 Sep 17;35(1):55-64

Mesh Tags

PMID: 18612082

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