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Genetics of gene expression and its effect on disease

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Authors
Emilsson, Valur
Thorleifsson, Gudmar
Zhang, Bin
Leonardson, Amy S
Zink, Florian
Zhu, Jun
Carlson, Sonia
Helgason, Agnar
Walters, G Bragi
Gunnarsdottir, Steinunn
Mouy, Magali
Steinthorsdottir, Valgerdur
Eiriksdottir, Gudrun H
Bjornsdottir, Gyda
Reynisdottir, Inga
Gudbjartsson, Daniel
Helgadottir, Anna
Jonasdottir, Aslaug
Jonasdottir, Adalbjorg
Styrkarsdottir, Unnur
Gretarsdottir, Solveig
Magnusson, Kristinn P
Stefansson, Hreinn
Fossdal, Ragnheidur
Kristjansson, Kristleifur
Gislason, Hjortur G
Stefansson, Tryggvi
Leifsson, Bjorn G
Thorsteinsdottir, Unnur
Lamb, John R
Gulcher, Jeffrey R
Reitman, Marc L
Kong, Augustine
Schadt, Eric E
Stefansson, Kari
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Issue Date
2008-03-27

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Citation
Nature 2008, 452(7186):423-8
Abstract
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/nature06758
ae974a485f413a2113503eed53cd6c53
10.1038/nature06758
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