Yosuke OmaeLicht Toyo-OkaHideki YanaiSupalert NedsuwanSukanya WattanapokayakitNusara SatproedpraiNat SmittipatPrasit PalittapongarnpimPathom SawanpanyalertWimala InunchotEkawat PasomsubNuanjun WichukchindaTaisei MushirodaMichiaki KuboKatsushi TokunagaSurakameth MahasirimongkolUniversity of TokyoThe Research Institute of Tuberculosis, Japan Anti-Tuberculosis AssociationThailand Ministry of Public HealthThailand National Center for Genetic Engineering and BiotechnologyMahidol UniversityThe Food and Drug Administration, Thailand Ministry of Public HealthRiken2018-12-212019-03-142018-12-212019-03-142017-12-01Journal of Human Genetics. Vol.62, No.12 (2017), 1015-10221435232X143451612-s2.0-85035232347https://repository.li.mahidol.ac.th/handle/123456789/41702Tuberculosis (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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/jhg.2017.82