Schurz, Haiko;
Naranbhai, Vivek;
Yates, Tom A;
Gilchrist, James;
Parks, Tom;
Dodd, Peter J;
Möller, Marlo;
... International Tuberculosis Host Genetics Consortium; + view all
(2024)
Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture.
eLife
, 13
, Article e84394. 10.7554/elife.84394.
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Abstract
The heritability of susceptibility to tuberculosis (TB) disease has been well recognized. Over 100 genes have been studied as candidates for TB susceptibility, and several variants were identified by genome-wide association studies (GWAS), but few replicate. We established the International Tuberculosis Host Genetics Consortium to perform a multi-ancestry meta-analysis of GWAS, including 14,153 cases and 19,536 controls of African, Asian, and European ancestry. Our analyses demonstrate a substantial degree of heritability (pooled polygenic h2 = 26.3%, 95% CI 23.7–29.0%) for susceptibility to TB that is shared across ancestries, highlighting an important host genetic influence on disease. We identified one global host genetic correlate for TB at genome-wide significance (p<5 × 10-8) in the human leukocyte antigen (HLA)-II region (rs28383206, p-value=5.2 × 10-9) but failed to replicate variants previously associated with TB susceptibility. These data demonstrate the complex shared genetic architecture of susceptibility to TB and the importance of large-scale GWAS analysis across multiple ancestries experiencing different levels of infection pressure.
| Type: | Article |
|---|---|
| Title: | Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/elife.84394 |
| Publisher version: | https://doi.org/10.7554/elife.84394 |
| Language: | English |
| Additional information: | Copyright © 2024, Schurz et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10185643 |
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