Genetics of gene expression and its effect on disease

被引：983

作者：

Emilsson, Valur ^{[1
,2
]}

Thorleifsson, Gudmar ^{[1
]}

Zhang, Bin ^{[2
]}

Leonardson, Amy S. ^{[2
]}

Zink, Florian ^{[1
]}

Zhu, Jun ^{[2
]}

Carlson, Sonia ^{[2
]}

Helgason, Agnar ^{[1
]}

Walters, G. Bragi ^{[1
]}

Gunnarsdottir, Steinunn ^{[1
]}

Mouy, Magali ^{[1
]}

Steinthorsdottir, Valgerdur ^{[1
]}

Eiriksdottir, Gudrun H. ^{[1
]}

Bjornsdottir, Gyda ^{[1
]}

Reynisdottir, Inga ^{[1
]}

Gudbjartsson, Daniel ^{[1
]}

Helgadottir, Anna ^{[1
]}

Jonasdottir, Aslaug ^{[1
]}

Jonasdottir, Adalbjorg ^{[1
]}

Styrkarsdottir, Unnur ^{[1
]}

Gretarsdottir, Solveig ^{[1
]}

Magnusson, Kristinn P. ^{[1
]}

Stefansson, Hreinn ^{[1
]}

Fossdal, Ragnheidur ^{[1
]}

Kristjansson, Kristleifur ^{[1
]}

Gislason, Hjortur G. ^{[3
]}

Stefansson, Tryggvi ^{[3
]}

Leifsson, Bjorn G. ^{[3
]}

Thorsteinsdottir, Unnur ^{[1
]}

Lamb, John R. ^{[2
]}

Gulcher, Jeffrey R. ^{[1
]}

Reitman, Marc L. ^{[4
]}

Kong, Augustine ^{[1
]}

Schadt, Eric E. ^{[2
]}

Stefansson, Kari ^{[1
]}

机构：

[1] deCODE Genet, IS-101 Reykjavik, Iceland

[2] Rosetta Inpharmat LLC, Seattle, WA 98109 USA

[3] Natl Univ Hosp Reykjavik, Dept Surg, IS-101 Reykjavik, Iceland

[4] Merck Res Labs, Rahway, NJ 07065 USA

来源：

NATURE | 2008年 / 452卷 / 7186期

关键词：

D O I：

10.1038/nature06758

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

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.

引用

页码：423 / U2

页数：8

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