Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture.

Autor:	Schurz H; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Naranbhai V; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.; Massachusetts General Hospital, Boston, United States.; Dana-Farber Cancer Institute, Boston, United States.; Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.; Harvard Medical School, Boston, United States., Yates TA; Division of Infection and Immunity, Faculty of Medical Sciences, University College London, London, United Kingdom., Gilchrist JJ; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.; Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Parks T; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.; Department of Infectious Diseases Imperial College London, London, United Kingdom., Dodd PJ; School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom., Möller M; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Hoal EG; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Morris AP; Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, United Kingdom., Hill AVS; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.; Jenner Institute, University of Oxford, Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Jan 15; Vol. 13. Date of Electronic Publication: 2024 Jan 15.
DOI:	10.7554/eLife.84394
Abstrakt:	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 h 2 = 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. Competing Interests: HS, VN, TY, JG, TP, PD, MM, EH, AM, AH No competing interests declared (© 2024, Schurz et al.)
Databáze:	MEDLINE
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