Background: There is reason to expect strong genetic influences on the risk of developing active pulmonary\r\ntuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies\r\n(GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically\r\ndissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a\r\nSoutheast Asian cohort from Indonesia.\r\nMethods: In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian\r\nsamples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In\r\nstage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals\r\nfrom the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB\r\nassociation in an independent Caucasian cohort (n = 3,760) from Russia.\r\nResults: Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal\r\nsignificance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1,\r\nDYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4.\r\nConclusions: Mechanisms of immune defense suggested by some of the identified genes exhibit biological\r\nplausibility and may suggest novel pathways involved in the host containment of infection with TB.
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