TY - JOUR
T1 - Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis
AU - Omae, Yosuke
AU - Toyo-Oka, Licht
AU - Yanai, Hideki
AU - Nedsuwan, Supalert
AU - Wattanapokayakit, Sukanya
AU - Satproedprai, Nusara
AU - Smittipat, Nat
AU - Palittapongarnpim, Prasit
AU - Sawanpanyalert, Pathom
AU - Inunchot, Wimala
AU - Pasomsub, Ekawat
AU - Wichukchinda, Nuanjun
AU - Mushiroda, Taisei
AU - Kubo, Michiaki
AU - Tokunaga, Katsushi
AU - Mahasirimongkol, Surakameth
N1 - Funding Information:
This work was supported by Japan International Cooperation Agency/Japan Agency for Medical Research and Development under Science and Technology Research Partnership for Sustainable Development.
Funding Information:
We thank all the participants in this study. This work was supported by Japan International Cooperation Agency/Japan Agency for Medical Research and Development under Science and Technology Research Partnership for Sustainable Development (SATREPS) project, Grant-in-Aid for Young Scientists (B) (JSPS KAKENHI grant number 15K19039), Grant-in-Aid for JSPS Fellows (grant number 25·10599) and Grant-in-Aid for Scientific Research (B) (grant numbers 15H05271, 24406010). Sample collection was also done by International Collaboration Research funding to the Research Institute of Tuberculosis—Japan Anti-Tuberculosis Association and Japan Science and Technology Agency-National Science and Technology Development Agency.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85035232347
UR - https://www.scopus.com/pages/publications/85035232347#tab=citedBy
U2 - 10.1038/jhg.2017.82
DO - 10.1038/jhg.2017.82
M3 - Article
C2 - 28878339
AN - SCOPUS:85035232347
SN - 1434-5161
VL - 62
SP - 1015
EP - 1022
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 12
ER -
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