A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians

Eileen Png*, Bachti Alisjahbana, Edhyana Sahiratmadja, Sangkot Marzuki, Ron Nelwan, Yanina Balabanova, Vladyslav Nikolayevskyy, Francis Drobniewski, Sergey Nejentsev, Iskandar Adnan, Esther van de Vosse, Martin L. Hibberd, Reinout van Crevel, Tom H.M. Ottenhoff, Mark Seielstad

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)


Background: There 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.Methods: In 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.Results: Our 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.Conclusions: Mechanisms 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.

Original languageEnglish
Article number5
JournalBMC Medical Genetics
Publication statusPublished - 13 Jan 2012

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Copyright 2012 Elsevier B.V., All rights reserved.


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