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Genetics of gene expression and its effect on disease

Author

Listed:
  • Valur Emilsson

    (deCODE genetics
    Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA)

  • Gudmar Thorleifsson

    (deCODE genetics)

  • Bin Zhang

    (Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA)

  • Amy S. Leonardson

    (Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA)

  • Florian Zink

    (deCODE genetics)

  • Jun Zhu

    (Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA)

  • Sonia Carlson

    (Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA)

  • Agnar Helgason

    (deCODE genetics)

  • G. Bragi Walters

    (deCODE genetics)

  • Steinunn Gunnarsdottir

    (deCODE genetics)

  • Magali Mouy

    (deCODE genetics)

  • Valgerdur Steinthorsdottir

    (deCODE genetics)

  • Gudrun H. Eiriksdottir

    (deCODE genetics)

  • Gyda Bjornsdottir

    (deCODE genetics)

  • Inga Reynisdottir

    (deCODE genetics)

  • Daniel Gudbjartsson

    (deCODE genetics)

  • Anna Helgadottir

    (deCODE genetics)

  • Aslaug Jonasdottir

    (deCODE genetics)

  • Adalbjorg Jonasdottir

    (deCODE genetics)

  • Unnur Styrkarsdottir

    (deCODE genetics)

  • Solveig Gretarsdottir

    (deCODE genetics)

  • Kristinn P. Magnusson

    (deCODE genetics)

  • Hreinn Stefansson

    (deCODE genetics)

  • Ragnheidur Fossdal

    (deCODE genetics)

  • Kristleifur Kristjansson

    (deCODE genetics)

  • Hjortur G. Gislason

    (National University Hospital)

  • Tryggvi Stefansson

    (National University Hospital)

  • Bjorn G. Leifsson

    (National University Hospital)

  • Unnur Thorsteinsdottir

    (deCODE genetics)

  • John R. Lamb

    (Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA)

  • Jeffrey R. Gulcher

    (deCODE genetics)

  • Marc L. Reitman

    (Merck Research Laboratories, Rahway, New Jersey 07065, USA)

  • Augustine Kong

    (deCODE genetics)

  • Eric E. Schadt

    (Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA)

  • Kari Stefansson

    (deCODE genetics)

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.

Suggested Citation

  • Valur Emilsson & Gudmar Thorleifsson & Bin Zhang & Amy S. Leonardson & Florian Zink & Jun Zhu & Sonia Carlson & Agnar Helgason & G. Bragi Walters & Steinunn Gunnarsdottir & Magali Mouy & Valgerdur Ste, 2008. "Genetics of gene expression and its effect on disease," Nature, Nature, vol. 452(7186), pages 423-428, March.
    • Handle: RePEc:nat:nature:v:452:y:2008:i:7186:d:10.1038_nature06758
    DOI: 10.1038/nature06758
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    Cited by:

    1. Dawei Li & Zedong Geng & Shixuan Xia & Hui Feng & Xiuhan Jiang & Hui Du & Pei Wang & Qun Lian & Yanhui Zhu & Yuxin Jia & Yao Zhou & Yaoyao Wu & Chenglong Huang & Guangtao Zhu & Yi Shang & Huihui Li & , 2024. "Integrative multi-omics analysis reveals genetic and heterotic contributions to male fertility and yield in potato," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Valur Emilsson & Elias F. Gudmundsson & Thorarinn Jonmundsson & Brynjolfur G. Jonsson & Michael Twarog & Valborg Gudmundsdottir & Zhiguang Li & Nancy Finkel & Stephen Poor & Xin Liu & Robert Esterberg, 2022. "A proteogenomic signature of age-related macular degeneration in blood," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Shichao Lin & Kun Yin & Yingkun Zhang & Fanghe Lin & Xiaoyong Chen & Xi Zeng & Xiaoxu Guo & Huimin Zhang & Jia Song & Chaoyong Yang, 2023. "Well-TEMP-seq as a microwell-based strategy for massively parallel profiling of single-cell temporal RNA dynamics," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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