Genetics of gene expression and its effect on disease.

Nature 2008 Mar 16;452(7186):423-8. Epub 2008 Mar 16.

deCODE genetics, 101 Reykjavik, Iceland.

Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.

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http://dx.doi.org/10.1038/nature06758DOI Listing
March 2008
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References

(Supplied by CrossRef)

EE Schadt et al.
Nature 2003

TR Golub et al.
Science 1999

JM Johnson et al.
Science 2003

DD Shoemaker et al.
Nature 2001

JB Welsh et al.
Proc. Natl Acad. Sci. USA 2001

EE Schadt et al.
Nature Genet. 2005

EE Schadt et al.
Sci. STKE 2005

J Zhu et al.
Cytogenet. Genome Res. 2004

RB Brem et al.
Science 2002

L Bystrykh et al.
Nature Genet. 2005

EJ Chesler et al.
Nature Genet. 2005

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