PMID- 38224499
OWN - NLM
STAT- MEDLINE
DCOM- 20240117
LR  - 20240210
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 13
DP  - 2024 Jan 15
TI  - Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis 
      identifies shared genetic architecture.
LID - 10.7554/eLife.84394 [doi]
LID - e84394
AB  - 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 x 10(-8)) 
      in the human leukocyte antigen (HLA)-II region (rs28383206, p-value=5.2 x 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.
CI  - (c) 2024, Schurz et al.
FAU - Schurz, Haiko
AU  - Schurz H
AUID- ORCID: 0000-0002-0009-3409
AD  - 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.
FAU - Naranbhai, Vivek
AU  - Naranbhai V
AD  - Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
AD  - Massachusetts General Hospital, Boston, United States.
AD  - Dana-Farber Cancer Institute, Boston, United States.
AD  - Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
AD  - Harvard Medical School, Boston, United States.
FAU - Yates, Tom A
AU  - Yates TA
AUID- ORCID: 0000-0002-6081-1767
AD  - Division of Infection and Immunity, Faculty of Medical Sciences, University 
      College London, London, United Kingdom.
FAU - Gilchrist, James J
AU  - Gilchrist JJ
AUID- ORCID: 0000-0003-2045-6788
AD  - Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
AD  - Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
FAU - Parks, Tom
AU  - Parks T
AD  - Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
AD  - Department of Infectious Diseases Imperial College London, London, United 
      Kingdom.
FAU - Dodd, Peter J
AU  - Dodd PJ
AD  - School of Health and Related Research, University of Sheffield, Sheffield, United 
      Kingdom.
FAU - Moller, Marlo
AU  - Moller M
AUID- ORCID: 0000-0002-0805-6741
AD  - 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.
FAU - Hoal, Eileen G
AU  - Hoal EG
AD  - 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.
FAU - Morris, Andrew P
AU  - Morris AP
AUID- ORCID: 0000-0002-6805-6014
AD  - Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal 
      Research, The University of Manchester, Manchester, United Kingdom.
FAU - Hill, Adrian V S
AU  - Hill AVS
AD  - Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
AD  - Jenner Institute, University of Oxford, Oxford, United Kingdom.
CN  - International Tuberculosis Host Genetics Consortium
LA  - eng
SI  - Dryad/10.5061/dryad.6wwpzgn2s
GR  - WT_/Wellcome Trust/United Kingdom
GR  - R01 AI136921/AI/NIAID NIH HHS/United States
GR  - MR/P022081/1/MRC_/Medical Research Council/United Kingdom
GR  - 21754/VAC_/Versus Arthritis/United Kingdom
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20240115
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
SB  - IM
UOF - doi: 10.1101/2022.08.26.22279009
MH  - Humans
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Polymorphism, Single Nucleotide
MH  - *Tuberculosis/genetics
MH  - Racial Groups/genetics
PMC - PMC10789494
OTO - NOTNLM
OT  - GWAS
OT  - HLA
OT  - genetics
OT  - genomics
OT  - human
OT  - meta-analysis
OT  - multi-ancestry
OT  - tuberculosis
COIS- HS, VN, TY, JG, TP, PD, MM, EH, AM, AH No competing interests declared
FIR - Schurz, Haiko
IR  - Schurz H
IRAD- 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.
FIR - Naranbhai, Vivek
IR  - Naranbhai V
IRAD- Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
IRAD- Massachusetts General Hospital, Boston, United States.
IRAD- Dana-Farber Cancer Institute, Boston, United States.
IRAD- Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
IRAD- Harvard Medical School, Boston, United States.
FIR - Yates, Tom A
IR  - Yates TA
IRAD- Division of Infection and Immunity, Faculty of Medical Sciences, University 
      College, London, United Kingdom.
FIR - Gilchrist, James J
IR  - Gilchrist JJ
IRAD- Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
IRAD- Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
FIR - Parks, Tom
IR  - Parks T
IRAD- Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
IRAD- Department of Infectious Diseases Imperial College London, London, United 
      Kingdom.
FIR - Dodd, Peter J
IR  - Dodd PJ
IRAD- Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal 
      Research, The University of Manchester, Manchester, United Kingdom.
FIR - Moller, Marlo
IR  - Moller M
IRAD- 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.
FIR - Hoal, Eileen G
IR  - Hoal EG
IRAD- 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.
FIR - Morris, Andrew P
IR  - Morris AP
IRAD- Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal 
      Research, The University of Manchester, Manchester, United Kingdom.
FIR - Hill, Adrian V S
IR  - Hill AVS
IRAD- Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
IRAD- Jenner Institute, University of Oxford, Oxford, United Kingdom.
FIR - van Crevel, Reinout
IR  - van Crevel R
IRAD- Department of Internal Medicine and Radboud Center for Infectious Diseases, 
      Radboud University Medical Center, Nijmegen, Netherlands.
IRAD- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, 
      University of Oxford, Oxford, United Kingdom.
FIR - van Laarhoven, Arjan
IR  - van Laarhoven A
IRAD- Department of Internal Medicine and Radboud Center for Infectious Diseases, 
      Radboud University Medical Center, Nijmegen, Netherlands.
FIR - Ottenhoff, Tom H M
IR  - Ottenhoff THM
IRAD- Head Lab Dept of Infectious Diseases; Head Group Immunology and Immunogenetics of 
      Bacterial Infectious Diseases Leiden University Medical Center, Leiden, 
      Netherlands.
FIR - Metspalu, Andres
IR  - Metspalu A
IRAD- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 
      Estonia.
FIR - Magi, Reedik
IR  - Magi R
IRAD- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 
      Estonia.
FIR - Meyer, Christian G
IR  - Meyer CG
IRAD- Institute of Tropical Medicine, Eberhard-Karls University Tubingen, Tubingen, 
      Germany.
IRAD- Faculty of Medicine, Duy Tan University, Da Nang, Viet Nam.
FIR - Ellis, Magda
IR  - Ellis M
IRAD- Tuberculosis Research Group, Centenary Institute, Sydney, Australia.
FIR - Thye, Thorsten
IR  - Thye T
IRAD- School of Health and Related Research, University of Sheffield, Sheffield, United 
      Kingdom.
FIR - Mahasirimongkol, Surakameth
IR  - Mahasirimongkol S
IRAD- Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
FIR - Pasomsub, Ekawat
IR  - Pasomsub E
IRAD- Virology Laboratory, Department of Pathology, Faculty of Medicine, Ramathibodi 
      Hospital, Mahidol University, Bangkok, Thailand.
FIR - Tokunaga, Katsushi
IR  - Tokunaga K
IRAD- Genome Medical Science Project, National Center for Global Health and Medicine, 
      Tokyo, Japan.
FIR - Omae, Yosuke
IR  - Omae Y
IRAD- Genome Medical Science Project, National Center for Global Health and Medicine, 
      Tokyo, Japan.
FIR - Yanai, Hideki
IR  - Yanai H
IRAD- Fukujuji Hospital and Research Institute of Tuberculosis, Japan Anti-Tuberculosis 
      Association, Kiyose, Japan.
FIR - Mushiroda, Taisei
IR  - Mushiroda T
IRAD- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
FIR - Kubo, Michiaki
IR  - Kubo M
IRAD- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
FIR - Takahashi, Atsushi
IR  - Takahashi A
IRAD- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
IRAD- Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama, Japan.
IRAD- Department of Genomic Medicine, Research Institute, National Cerebral and 
      Cardiovascular Center, Suita, Japan.
FIR - Kamatani, Yoichiro
IR  - Kamatani Y
IRAD- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
IRAD- Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama, Japan.
FIR - Alisjahbana, Bachti
IR  - Alisjahbana B
IRAD- Faculty of Medicine, Universitas Padjdjaran - Hasan Sadikin Hospital, Bandung, 
      Indonesia.
FIR - Liu, Wei
IR  - Liu W
IRAD- Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of 
      Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong 
      University - School of Medicine, Shanghai, China.
IRAD- National Tissue Engineering Center of China, Shanghai, China.
FIR - Sheng, A-Dong
IR  - Sheng AD
IRAD- National Clinical Research Center for Respiratory Diseases, National Key 
      Discipline of Pediatrics, Capital Medical University, Beijing, China.
IRAD- Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 
      Children's Hospital, National Center for Children's Health, Capital Medical 
      University, Beijing, China.
IRAD- Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing 
      Pediatric Research Institute, Beijing, China.
IRAD- Children's Hospital Affiliated to Zhengzhou University, Henan Children's 
      Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
FIR - Yang, Yurong
IR  - Yang Y
IRAD- Ningxia Medical University, Ningxia Hui Autonomous Region, Ningxia, China.
EDAT- 2024/01/15 18:44
MHDA- 2024/01/17 06:43
PMCR- 2024/01/15
CRDT- 2024/01/15 12:53
PHST- 2022/10/23 00:00 [received]
PHST- 2023/11/23 00:00 [accepted]
PHST- 2024/01/17 06:43 [medline]
PHST- 2024/01/15 18:44 [pubmed]
PHST- 2024/01/15 12:53 [entrez]
PHST- 2024/01/15 00:00 [pmc-release]
AID - 84394 [pii]
AID - 10.7554/eLife.84394 [doi]
PST - epublish
SO  - Elife. 2024 Jan 15;13:e84394. doi: 10.7554/eLife.84394.