TY - JOUR
T1 - Genetics of gene expression and its effect on disease
AU - Emilsson, Valur
AU - Thorleifsson, Gudmar
AU - Zhang, Bin
AU - Leonardson, Amy S.
AU - Zink, Florian
AU - Zhu, Jun
AU - Carlson, Sonia
AU - Helgason, Agnar
AU - Walters, G. Bragi
AU - Gunnarsdottir, Steinunn
AU - Mouy, Magali
AU - Steinthorsdottir, Valgerdur
AU - Eiriksdottir, Gudrun H.
AU - Bjornsdottir, Gyda
AU - Reynisdottir, Inga
AU - Gudbjartsson, Daniel
AU - Helgadottir, Anna
AU - Jonasdottir, Aslaug
AU - Jonasdottir, Adalbjorg
AU - Styrkarsdottir, Unnur
AU - Gretarsdottir, Solveig
AU - Magnusson, Kristinn P.
AU - Stefansson, Hreinn
AU - Fossdal, Ragnheidur
AU - Kristjansson, Kristleifur
AU - Gislason, Hjortur G.
AU - Stefansson, Tryggvi
AU - Leifsson, Bjorn G.
AU - Thorsteinsdottir, Unnur
AU - Lamb, John R.
AU - Gulcher, Jeffrey R.
AU - Reitman, Marc L.
AU - Kong, Augustine
AU - Schadt, Eric E.
AU - Stefansson, Kari
PY - 2008/3/27
Y1 - 2008/3/27
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/41349095280
U2 - 10.1038/nature06758
DO - 10.1038/nature06758
M3 - Article
C2 - 18344981
AN - SCOPUS:41349095280
SN - 0028-0836
VL - 452
SP - 423
EP - 428
JO - Nature
JF - Nature
IS - 7186
ER -