Year-end Sale % OFF 
Abstract
BackgroundThere is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia.MethodsIn stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia.ResultsOur study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4.ConclusionsMechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB.
Highlights
There is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals
A genome wide association study (GWAS), by contrast, can scan nearly the entire genome for variants associated with a phenotype, free from limiting hypotheses of biological plausibility
For all cases in this study, diagnosis was further confirmed by sputum culture of M. tuberculosis
Summary
There is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Because the infection causes such a burden of disease in those unable to contain the infection, it is important to discover underlying mechanisms to aid the development of more effective interventions such as Studies of heritability using twins and other familial designs have convincingly implicated a genetic component contributing to outcomes of TB infection [4,5,6,7]. This has encouraged us to conduct a genome-wide search for genes relevant to pulmonary TB susceptibility and active disease. The variant implicated, rs4331426, lies within a gene-desert, with the risk allele relatively common in the African population studied, though it is found at much lower frequencies in other populations, making it difficult to replicate the reported association outside Africa [10]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
