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 journalArticleAcademicpeer-review

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 languageEnglish
Article number3765
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019
Externally publishedYes

Cite this

Luo, Y., Suliman, S., Asgari, S., Amariuta, T., Baglaenko, Y., Martínez-Bonet, M., ... Raychaudhuri, S. (2019). Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians. Nature Communications, 10(1), [3765]. https://doi.org/10.1038/s41467-019-11664-1