1. deCODE genetics, 101 Reykjavik, Iceland
2. Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA
3. Department of Surgery, National University Hospital, 101 Reykjavik, Iceland
4. Merck Research Laboratories, Rahway, New Jersey 07065, USA
5. These authors contributed equally to this work.

Correspondence to: Eric E. Schadt^2,5Kari Stefansson^1,5 Correspondence and requests for materials should be addressed to K.S. (Email: kari.stefansson@decode.is) or E.E.S. (Email: eric_schadt@merck.com).

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.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.