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The Role of Host Genetics (and Genomics) in Tuberculosis

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  • Author: Vivek Naranbhai1
  • Editors: William R. Jacobs Jr.2, Helen McShane3, Valerie Mizrahi4, Ian M. Orme5
    Affiliations: 1: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire OX37BN, United Kingdom; Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa; 2: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 3: University of Oxford, Oxford OX3 7DQ, United Kingdom; 4: University of Cape Town, Rondebosch 7701, South Africa; 5: Colorado State University, Fort Collins, CO 80523
  • Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0011-2016
  • Received 26 January 2016 Accepted 31 March 2016 Published 28 October 2016
  • Vivek Naranbhai, vivekn@well.ox.ac.uk
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  • Abstract:

    Familial risk of tuberculosis (TB) has been recognized for centuries. Largely through studies of mono- and dizygotic twin concordance rates, studies of families with Mendelian susceptibility to mycobacterial disease, and candidate gene studies performed in the 20th century, it was recognized that susceptibility to TB disease has a substantial host genetic component. Limitations in candidate gene studies and early linkage studies made the robust identification of specific loci associated with disease challenging, and few loci have been convincingly associated across multiple populations. Genome-wide and transcriptome-wide association studies, based on microarray (commonly known as genechip) technologies, conducted in the past decade have helped shed some light on pathogenesis but only a handful of new pathways have been identified. This apparent paradox, of high heritability but few replicable associations, has spurred a new wave of collaborative global studies. This review aims to comprehensively review the heritability of TB, critically review the host genetic and transcriptomic correlates of disease, and highlight current studies and future prospects in the study of host genomics in TB. An implicit goal of elucidating host genetic correlates of susceptibility to infection or TB disease is to identify pathophysiological features amenable to translation to new preventive, diagnostic, or therapeutic interventions. The translation of genomic insights into new clinical tools is therefore also discussed.

  • Citation: Naranbhai V. 2016. The Role of Host Genetics (and Genomics) in Tuberculosis. Microbiol Spectrum 4(5):TBTB2-0011-2016. doi:10.1128/microbiolspec.TBTB2-0011-2016.

Key Concept Ranking

Tumor Necrosis Factor alpha
Transforming Growth Factor beta


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