Genetics of gene expression and its effect on disease

Valur Emilsson, Gudmar Thorleifsson, Bin Zhang, Amy S. Leonardson, Florian Zink, Jun Zhu, Sonia Carlson, Agnar Helgason, G. Bragi Walters, Steinunn Gunnarsdottir, Magali Mouy, Valgerdur Steinthorsdottir, Gudrun H. Eiriksdottir, Gyda Bjornsdottir, Inga Reynisdottir, Daniel Gudbjartsson, Anna Helgadottir, Aslaug Jonasdottir, Adalbjorg Jonasdottir, Unnur Styrkarsdottir, Solveig Gretarsdottir, Kristinn P. Magnusson, Hreinn Stefansson, Ragnheidur Fossdal, Kristleifur Kristjansson, Hjortur G. Gislason, Tryggvi Stefansson, Bjorn G. Leifsson, Unnur Thorsteinsdottir, John R. Lamb, Jeffrey R. Gulcher, Marc L. Reitman, Augustine Kong, Eric E. Schadt () and Kari Stefansson ()
Additional contact information
Valur Emilsson: deCODE genetics
Gudmar Thorleifsson: deCODE genetics
Bin Zhang: Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA
Amy S. Leonardson: Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA
Florian Zink: deCODE genetics
Jun Zhu: Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA
Sonia Carlson: Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA
Agnar Helgason: deCODE genetics
G. Bragi Walters: deCODE genetics
Steinunn Gunnarsdottir: deCODE genetics
Magali Mouy: deCODE genetics
Valgerdur Steinthorsdottir: deCODE genetics
Gudrun H. Eiriksdottir: deCODE genetics
Gyda Bjornsdottir: deCODE genetics
Inga Reynisdottir: deCODE genetics
Daniel Gudbjartsson: deCODE genetics
Anna Helgadottir: deCODE genetics
Aslaug Jonasdottir: deCODE genetics
Adalbjorg Jonasdottir: deCODE genetics
Unnur Styrkarsdottir: deCODE genetics
Solveig Gretarsdottir: deCODE genetics
Kristinn P. Magnusson: deCODE genetics
Hreinn Stefansson: deCODE genetics
Ragnheidur Fossdal: deCODE genetics
Kristleifur Kristjansson: deCODE genetics
Hjortur G. Gislason: National University Hospital
Tryggvi Stefansson: National University Hospital
Bjorn G. Leifsson: National University Hospital
Unnur Thorsteinsdottir: deCODE genetics
John R. Lamb: Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA
Jeffrey R. Gulcher: deCODE genetics
Marc L. Reitman: Merck Research Laboratories, Rahway, New Jersey 07065, USA
Augustine Kong: deCODE genetics
Eric E. Schadt: Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA
Kari Stefansson: deCODE genetics

Nature, 2008, vol. 452, issue 7186, 423-428

Abstract: 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.

Date: 2008
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DOI: 10.1038/nature06758

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