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Systems Genetics as a Tool to Identify Master Genetic Regulators in Complex Disease

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Systems Genetics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1488))

Abstract

Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease. In addition, systems genetics has proven useful in the discovery of master trans-acting genetic regulators of functional networks and pathways, which in many cases revealed unexpected gene targets for disease. Here we detail the central components of a fully integrated systems genetics approach to complex disease, starting from assessment of genetic and gene expression variation, linking DNA sequence variation to mRNA (expression QTL mapping), gene regulatory network analysis and mapping the genetic control of regulatory networks. By summarizing a few illustrative (and successful) examples, we highlight how different data-modeling strategies can be effectively integrated in a systems genetics study.

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Acknowledgments

We acknowledge funding from the British Heart Foundation (Ph.D. Studentship grant FS/11/25/28740; E.P. and A.M.M.), the European Union FP7 (ERG-239158, CardioNeT-ITN-289600, F.P.), Kidney Research UK (RP9/2013) (J.B.) and Medical Research Council Grant MR/M004716/1 (J.B. and E.P.) and Duke-NUS Graduate Medical School Singapore (E.P.).

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Authors and Affiliations

  1. Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore

    Aida Moreno-Moral & Enrico Petretto

  2. National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Hammersmith Campus, Imperial Centre for Translational and Experimental Medicine, London, UK

    Francesco Pesce

  3. Centre for Complement and Inflammation Research, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK

    Jacques Behmoaras

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  1. Aida Moreno-Moral
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  2. Francesco Pesce
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  3. Jacques Behmoaras
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  4. Enrico Petretto
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Corresponding author

Correspondence to Enrico Petretto .

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Editors and Affiliations

  1. Department of Infection Genetics, Helmholtz Centre for Infection Research & University of Veterinary Medicine Hannover, Braunschweig, Niedersachsen, Germany

    Klaus Schughart

  2. Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA

    Robert W. Williams

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Moreno-Moral, A., Pesce, F., Behmoaras, J., Petretto, E. (2017). Systems Genetics as a Tool to Identify Master Genetic Regulators in Complex Disease. In: Schughart, K., Williams, R. (eds) Systems Genetics. Methods in Molecular Biology, vol 1488. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6427-7_16

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  • DOI: https://doi.org/10.1007/978-1-4939-6427-7_16

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  • Print ISBN: 978-1-4939-6425-3

  • Online ISBN: 978-1-4939-6427-7

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