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Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis
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Document Title
Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis
Author
Omae Y.,Toyo-Oka L.,Yanai H.,Nedsuwan S.,Wattanapokayakit S.,Satproedprai N.,Smittipat N.,Palittapongarnpim P.,Sawanpanyalert P.,Inunchot W.,Pasomsub E.,Wichukchinda N.,Mushiroda T.,Kubo M.,Tokunaga K.,Mahasirimongkol S.
Name from Authors Collection
Affiliations
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Fukujuji Hospital and Research Institute of Tuberculosis (RIT), Japan Anti-Tuberculosis Association, Kiyose, Japan; Chiangrai Prachanukroh Hospital, Ministry of Public Health, Chiang Rai, Thailand; Medical Genetics Center, Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Tuberculosis Research Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Food and Drug Administration, Ministry of Public Health, Nonthaburi, Thailand; Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Type
Article
Source Title
Journal of Human Genetics
ISSN
14345161
Year
2017
Volume
62
Issue
12
Page
1015-1022
Open Access
All Open Access, Hybrid Gold, Green
Publisher
Nature Publishing Group
DOI
10.1038/jhg.2017.82
Abstract
Tuberculosis (TB) is known to be affected by host genetic factors. We reported a specific genetic risk factor through a genome-wide association study (GWAS) that focused on young age onset TB. In this study, we further focused on the heterogeneity of Mycobacterium tuberculosis (M. tb) lineages and assessed its possible interaction with age at onset on host genetic factors. We identified the pathogen lineage in 686 Thai TB cases and GWAS stratified by both infected pathogen lineage information and age at onset revealed a genome-wide significant association of one single-nucleotide polymorphism (SNP) on chromosome 1p13, which was specifically associated with non-Beijing lineage-infected old age onset cases (P=2.54E-08, OR=1.74 (95% CI=1.43-2.12)), when we compared them to the population-matched healthy controls. This SNP locates near the CD53 gene, which encodes a leukocyte surface glycoprotein. Interestingly, the expression of CD53 was also correlated with the patients' active TB status. This is the first report of a pathogen lineage-based genome-wide association study. The results suggested that host genetic risk in TB is depended upon the pathogen genetic background and demonstrate the importance of analyzing the interaction between host and pathogen genomes in TB.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
License
CC BY-NC-SA
Rights
Author
Publication Source
Scopus