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Title: Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis
Authors: Yosuke Omae
Licht Toyo-Oka
Hideki Yanai
Supalert Nedsuwan
Sukanya Wattanapokayakit
Nusara Satproedprai
Nat Smittipat
Prasit Palittapongarnpim
Pathom Sawanpanyalert
Wimala Inunchot
Ekawat Pasomsub
Nuanjun Wichukchinda
Taisei Mushiroda
Michiaki Kubo
Katsushi Tokunaga
Surakameth Mahasirimongkol
University of Tokyo
The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association
Thailand Ministry of Public Health
Thailand National Center for Genetic Engineering and Biotechnology
Mahidol University
The Food and Drug Administration, Thailand Ministry of Public Health
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Dec-2017
Citation: Journal of Human Genetics. Vol.62, No.12 (2017), 1015-1022
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.
ISSN: 1435232X
Appears in Collections:Scopus 2016-2017

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