Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

Yang Luo; Sara Suliman; Samira Asgari; Tiffany Amariuta; Yuriy Baglaenko; Marta Martínez-Bonet; Kazuyoshi Ishigaki; Maria Gutierrez-Arcelus; Roger Calderon; Leonid Lecca; Segundo R. León; Judith Jimenez; Rosa Yataco; Carmen Contreras; Jerome T. Galea; Mercedes Becerra; Sergey Nejentsev; Peter A. Nigrovic; D. Branch Moody; Megan B. Murray; Soumya Raychaudhuri

doi:10.1038/s41467-019-11664-1

Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

Yang Luo, Sara Suliman, Samira Asgari, Tiffany Amariuta, Yuriy Baglaenko, Marta Martínez-Bonet, Kazuyoshi Ishigaki, Maria Gutierrez-Arcelus, Roger Calderon, Leonid Lecca, Segundo R. León, Judith Jimenez, Rosa Yataco, Carmen Contreras, Jerome T. Galea, Mercedes Becerra, Sergey Nejentsev, Peter A. Nigrovic, D. Branch Moody, Megan B. MurraySoumya Raychaudhuri

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

Abstract

Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5–15% will develop active tuberculosis (TB). Approximately half will progress to active TB within the first 18 months after infection, presumably because they fail to mount an effective initial immune response. Here, in a genome-wide genetic study of early TB progression, we genotype 4002 active TB cases and their household contacts in Peru. We quantify genetic heritability (hg2) of early TB progression to be 21.2% (standard error 0.08). This suggests TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases. We identify a novel association between early TB progression and variants located in a putative enhancer region on chromosome 3q23 (rs73226617, OR = 1.18; P = 3.93 × 10⁻⁸). With in silico and in vitro analyses we identify rs73226617 or rs148722713 as the likely functional variant and ATP1B3 as a potential causal target gene with monocyte specific function.

Original language	English
Article number	3765
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11664-1
Publication status	Published - 2019 Dec 1
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-019-11664-1

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Luo, Y., Suliman, S., Asgari, S., Amariuta, T., Baglaenko, Y., Martínez-Bonet, M., Ishigaki, K., Gutierrez-Arcelus, M., Calderon, R., Lecca, L., León, S. R., Jimenez, J., Yataco, R., Contreras, C., Galea, J. T., Becerra, M., Nejentsev, S., Nigrovic, P. A., Moody, D. B., ... Raychaudhuri, S. (2019). Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians. Nature communications, 10(1), Article 3765. https://doi.org/10.1038/s41467-019-11664-1

Luo, Y, Suliman, S, Asgari, S, Amariuta, T, Baglaenko, Y, Martínez-Bonet, M, Ishigaki, K, Gutierrez-Arcelus, M, Calderon, R, Lecca, L, León, SR, Jimenez, J, Yataco, R, Contreras, C, Galea, JT, Becerra, M, Nejentsev, S, Nigrovic, PA, Moody, DB, Murray, MB & Raychaudhuri, S 2019, 'Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians', Nature communications, vol. 10, no. 1, 3765. https://doi.org/10.1038/s41467-019-11664-1

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abstract = "Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5–15% will develop active tuberculosis (TB). Approximately half will progress to active TB within the first 18 months after infection, presumably because they fail to mount an effective initial immune response. Here, in a genome-wide genetic study of early TB progression, we genotype 4002 active TB cases and their household contacts in Peru. We quantify genetic heritability (hg2) of early TB progression to be 21.2% (standard error 0.08). This suggests TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases. We identify a novel association between early TB progression and variants located in a putative enhancer region on chromosome 3q23 (rs73226617, OR = 1.18; P = 3.93 × 10−8). With in silico and in vitro analyses we identify rs73226617 or rs148722713 as the likely functional variant and ATP1B3 as a potential causal target gene with monocyte specific function.",

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AU - Baglaenko, Yuriy

AU - Martínez-Bonet, Marta

AU - Ishigaki, Kazuyoshi

AU - Gutierrez-Arcelus, Maria

AU - Calderon, Roger

AU - Lecca, Leonid

AU - León, Segundo R.

AU - Jimenez, Judith

AU - Yataco, Rosa

AU - Contreras, Carmen

AU - Galea, Jerome T.

AU - Becerra, Mercedes

AU - Nejentsev, Sergey

AU - Nigrovic, Peter A.

AU - Moody, D. Branch

AU - Murray, Megan B.

AU - Raychaudhuri, Soumya

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AB - Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5–15% will develop active tuberculosis (TB). Approximately half will progress to active TB within the first 18 months after infection, presumably because they fail to mount an effective initial immune response. Here, in a genome-wide genetic study of early TB progression, we genotype 4002 active TB cases and their household contacts in Peru. We quantify genetic heritability (hg2) of early TB progression to be 21.2% (standard error 0.08). This suggests TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases. We identify a novel association between early TB progression and variants located in a putative enhancer region on chromosome 3q23 (rs73226617, OR = 1.18; P = 3.93 × 10−8). With in silico and in vitro analyses we identify rs73226617 or rs148722713 as the likely functional variant and ATP1B3 as a potential causal target gene with monocyte specific function.

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Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

Abstract

ASJC Scopus subject areas

UN SDGs

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