TY - JOUR
T1 - Genetics of human susceptibility to active and latent tuberculosis
T2 - present knowledge and future perspectives
AU - Abel, Laurent
AU - Fellay, Jacques
AU - Haas, David W.
AU - Schurr, Erwin
AU - Srikrishna, Geetha
AU - Urbanowski, Michael
AU - Chaturvedi, Nimisha
AU - Srinivasan, Sudha
AU - Johnson, Daniel H.
AU - Bishai, William R.
N1 - Funding Information:
We thank all colleagues of our laboratories and workshop participants for their discussions and contributions. LA was supported in part by grants from the European Research Council (ERC-2010-AdG-268777), the French National Agency for Research (TBPATHGEN-ANR-14-CE14-0007-01), the St Giles Foundation, the Rockefeller University, and the National Institute of Allergy and Infectious Diseases (U01AI088685, R01AI089970, U19AI111143, and R37AI095983). JF is supported by a Professorship grant from the Swiss National Science Foundation (PP00P3_133703). The work of DWH was supported in part by grants from the National Institutes of Health (R01 AI077505 and P30 AI110527). Work in the laboratory of ES is supported by a Foundation grant of the Canadian Institutes of Health Research (FDN-1433322) and a grant from the National Institutes of Health (RO1AI124349). WRB acknowledges the support of the National Institutes of Health grants (AI36973 and AI37856), and funding from the Howard Hughes Medical Institute.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/3
Y1 - 2018/3
N2 - Tuberculosis is an ancient human disease, estimated to have originated and evolved over thousands of years alongside modern human populations. Despite considerable advances in disease control, tuberculosis remains one of the world's deadliest communicable diseases with 10 million incident cases and 1·8 million deaths in 2015 alone based on the annual WHO report, due to inadequate health service resources in less-developed regions of the world, and exacerbated by the HIV/AIDS pandemic and emergence of multidrug-resistant strains of Mycobacterium tuberculosis. Recent findings from studies of tuberculosis infection and of patients with Mendelian predisposition to severe tuberculosis have started to reveal human loci influencing tuberculosis outcomes. In this Review, we assess the current understanding of the contribution of host genetics to disease susceptibility and to drug treatment. Despite remarkable progress in technology, only a few associated genetic variants have so far been identified, strongly indicating the need for larger global studies that investigate both common and under-represented rare variants to develop new approaches to combat the disease. Pharmacogenomic discoveries are also likely to lead to more efficient drug design and development, and ultimately safer and more effective therapies for tuberculosis.
AB - Tuberculosis is an ancient human disease, estimated to have originated and evolved over thousands of years alongside modern human populations. Despite considerable advances in disease control, tuberculosis remains one of the world's deadliest communicable diseases with 10 million incident cases and 1·8 million deaths in 2015 alone based on the annual WHO report, due to inadequate health service resources in less-developed regions of the world, and exacerbated by the HIV/AIDS pandemic and emergence of multidrug-resistant strains of Mycobacterium tuberculosis. Recent findings from studies of tuberculosis infection and of patients with Mendelian predisposition to severe tuberculosis have started to reveal human loci influencing tuberculosis outcomes. In this Review, we assess the current understanding of the contribution of host genetics to disease susceptibility and to drug treatment. Despite remarkable progress in technology, only a few associated genetic variants have so far been identified, strongly indicating the need for larger global studies that investigate both common and under-represented rare variants to develop new approaches to combat the disease. Pharmacogenomic discoveries are also likely to lead to more efficient drug design and development, and ultimately safer and more effective therapies for tuberculosis.
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U2 - 10.1016/S1473-3099(17)30623-0
DO - 10.1016/S1473-3099(17)30623-0
M3 - Review article
C2 - 29111156
AN - SCOPUS:85032340890
SN - 1473-3099
VL - 18
SP - e64-e75
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 3
ER -