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.

To maximize the potential of genomics in medicine, it is essential to establish databases of genomic variants for ethno‐geographic groups that can be used for filtering and prioritizing candidate pathogenic variants. Populations with non‐European ancestry are poorly represented among current genomic variant databases. Here, we report the first high‐density survey of genomic variants for the Thai population, the Thai Reference Exome (T‐REx) variant database. T‐REx comprises exome sequencing data of 1092 unrelated Thai individuals. The targeted exome regions common among four capture platforms cover 30.04 Mbp on autosomes and chromosome X. 345 681 short variants (18.27% of which are novel) and 34 907 copy number variations were found. Principal component analysis on 38 469 single nucleotide variants present worldwide showed that the Thai population is most genetically similar to East and Southeast Asian populations. Moreover, unsupervised clustering revealed six Thai subpopulations consistent with the evidence of gene flow from neighboring populations. The prevalence of common pathogenic variants in T‐REx was investigated in detail, which revealed subpopulation‐specific patterns, in particular variants associated with erythrocyte disorders such as the HbE variant in HBB and the Viangchan variant in G6PD. T‐REx serves as a pivotal addition to the current databases for genomic medicine.

Dengue virus (DENV) infection can cause a self-limiting disease (dengue fever) or a more severe clinical presentation known as dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Furthermore, data from recent dengue epidemics in Brazil indicate that the neurological manifestations are becoming more prevalent. However, the neuropathogenesis of dengue are not well understood. The balance between viral replication efficiency and innate immunity--in opposition during the early stages of infection--determines the clinical outcome of DENV infection. In this study, we investigated the effects of DENV infection on the transcription profile of the central nervous system (CNS) of mice. We observed in infected mice the up-regulation of 151 genes possibly involved in neuropathogenesis of dengue. Conversely, they may have a protective effect. Ingenuity Systems software analysis demonstrated, that the main pathways modulated by DENV infection in the mouse CNS are involved in interferon signaling and antigen presentation.