Genetics of gene expression and its effect on disease

• Published in: Nature
• Main 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
• Other Authors: deCODE genetics, 101 Reykjavik, Iceland.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Publishing Group 2008
• Subjects: Adipose Tissue; Adolescent; Adult; Aged; 80 and over; Animals; Blood; Body Mass Index; Cohort Studies; European Continental Ancestry Group; Female; Gene Expression Profiling; Gene Expression Regulation; Genome; Human; Humans; Iceland; Lod Score; Male; Mice; Middle Aged; Obesity; Polymorphism; Single Nucleotide; Quantitative Trait Loci; Sample Size; Waist-Hip Ratio
• Online Access: http://hdl.handle.net/2336/33894; https://doi.org/10.1038/nature06758

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field 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.