Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture
Issued Date
2024-01-01
Resource Type
eISSN
2050084X
Scopus ID
2-s2.0-85182540600
Pubmed ID
38224499
Journal Title
eLife
Volume
13
Rights Holder(s)
SCOPUS
Bibliographic Citation
eLife Vol.13 (2024)
Suggested Citation
Schurz H., Naranbhai V., Yates T.A., Gilchrist J.J., Parks T., Dodd P.J., Möller M., Hoal E.G., Morris A.P., Hill A.V.S., van Crevel R., van Laarhoven A., Ottenhoff T.H.M., Metspalu A., Magi R., Meyer C.G., Ellis M., Thye T., Mahasirimongkol S., Pasomsub E., Tokunaga K., Omae Y., Yanai H., Mushiroda T., Kubo M., Takahashi A., Kamatani Y., Alisjahbana B., Liu W., Sheng A.D., Yang Y. Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture. eLife Vol.13 (2024). doi:10.7554/eLife.84394 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101280
Title
Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture
Author(s)
Schurz H.
Naranbhai V.
Yates T.A.
Gilchrist J.J.
Parks T.
Dodd P.J.
Möller M.
Hoal E.G.
Morris A.P.
Hill A.V.S.
van Crevel R.
van Laarhoven A.
Ottenhoff T.H.M.
Metspalu A.
Magi R.
Meyer C.G.
Ellis M.
Thye T.
Mahasirimongkol S.
Pasomsub E.
Tokunaga K.
Omae Y.
Yanai H.
Mushiroda T.
Kubo M.
Takahashi A.
Kamatani Y.
Alisjahbana B.
Liu W.
Sheng A.D.
Yang Y.
Naranbhai V.
Yates T.A.
Gilchrist J.J.
Parks T.
Dodd P.J.
Möller M.
Hoal E.G.
Morris A.P.
Hill A.V.S.
van Crevel R.
van Laarhoven A.
Ottenhoff T.H.M.
Metspalu A.
Magi R.
Meyer C.G.
Ellis M.
Thye T.
Mahasirimongkol S.
Pasomsub E.
Tokunaga K.
Omae Y.
Yanai H.
Mushiroda T.
Kubo M.
Takahashi A.
Kamatani Y.
Alisjahbana B.
Liu W.
Sheng A.D.
Yang Y.
Author's Affiliation
RIKEN Center for Integrative Medical Sciences
Ramathibodi Hospital
Faculty of Medicine, Dentistry and Health
UCL Faculty of Medical Sciences
The Jenner Institute
Duy Tan University
The Wellcome Centre for Human Genetics
Centre for the AIDS Programme of Research in South Africa
Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine
Beijing Tiantan Hospital, Capital Medical University
Beijing Children's Hospital, Capital Medical University
Hasan Sadikin Hospital
Tartu Ülikooli Genoomika Instituut
Massachusetts General Hospital
National Center for Global Health and Medicine
Zhengzhou University
Ningxia Medical University
Eberhard Karls Universität Tübingen
National Cerebral and Cardiovascular Center
Thailand Ministry of Public Health
Leids Universitair Medisch Centrum
Imperial College London
Dana-Farber Cancer Institute
The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association
Nuffield Department of Medicine
The University of Manchester
Centenary Institute of Cancer Medicine and Cell Biology
Harvard Medical School
University of Oxford Medical Sciences Division
Radboud University Medical Center
Stellenbosch University
National Tissue Engineering Center of China
Beijing Pediatric Research Institute
Ramathibodi Hospital
Faculty of Medicine, Dentistry and Health
UCL Faculty of Medical Sciences
The Jenner Institute
Duy Tan University
The Wellcome Centre for Human Genetics
Centre for the AIDS Programme of Research in South Africa
Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine
Beijing Tiantan Hospital, Capital Medical University
Beijing Children's Hospital, Capital Medical University
Hasan Sadikin Hospital
Tartu Ülikooli Genoomika Instituut
Massachusetts General Hospital
National Center for Global Health and Medicine
Zhengzhou University
Ningxia Medical University
Eberhard Karls Universität Tübingen
National Cerebral and Cardiovascular Center
Thailand Ministry of Public Health
Leids Universitair Medisch Centrum
Imperial College London
Dana-Farber Cancer Institute
The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association
Nuffield Department of Medicine
The University of Manchester
Centenary Institute of Cancer Medicine and Cell Biology
Harvard Medical School
University of Oxford Medical Sciences Division
Radboud University Medical Center
Stellenbosch University
National Tissue Engineering Center of China
Beijing Pediatric Research Institute
Corresponding Author(s)
Other Contributor(s)
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.