Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis

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

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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.

Original languageEnglish
Pages (from-to)1015-1022
Number of pages8
JournalJournal of Human Genetics
Volume62
Issue number12
DOIs
Publication statusPublished - 01-12-2017

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All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

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. (2017). Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis. Journal of Human Genetics, 62(12), 1015-1022. https://doi.org/10.1038/jhg.2017.82