Genetics of gene expression and its effect on disease
| Autor: | Sonia Carlson, Steinunn Gunnarsdottir, Jeffrey R. Gulcher, Gyda Bjornsdottir, Marc L. Reitman, Valgerdur Steinthorsdottir, Daniel F. Gudbjartsson, Amy Leonardson, Hjörtur Gislason, Unnur Styrkarsdottir, Augustine Kong, Ragnheidur Fossdal, John Lamb, Inga Reynisdottir, Gudrun H. Eiriksdottir, Kristleifur Kristjansson, Valur Emilsson, Jun Zhu, Kristinn P. Magnusson, Björn Geir Leifsson, Aslaug Jonasdottir, Agnar Helgason, Anna Helgadottir, Eric E. Schadt, Solveig Gretarsdottir, Magali Mouy, Kari Stefansson, Hreinn Stefansson, Gudmar Thorleifsson, Florian Zink, Bin Zhang, G. Bragi Walters, Tryggvi Stefansson, Adalbjorg Jonasdottir, Unnur Thorsteinsdottir |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Adolescent Quantitative Trait Loci Iceland Adipose tissue Single-nucleotide polymorphism Biology Quantitative trait locus Polymorphism Single Nucleotide White People Body Mass Index Cohort Studies Mice Animals Humans Obesity Association mapping Gene Aged Aged 80 and over Genetics Multidisciplinary Genome Human Waist-Hip Ratio Gene Expression Profiling Middle Aged Phenotype Gene expression profiling Blood Adipose Tissue Gene Expression Regulation Sample Size Female Lod Score Functional genomics |
| Zdroj: | Nature. 452:423-428 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature06758 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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