Open Access Highly Accessed Research article

A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians

Eileen Png12*, Bachti Alisjahbana34, Edhyana Sahiratmadja45, Sangkot Marzuki6, Ron Nelwan7, Yanina Balabanova89, Vladyslav Nikolayevskyy9, Francis Drobniewski9, Sergey Nejentsev10, Iskandar Adnan6, Esther van de Vosse11, Martin L Hibberd2, Reinout van Crevel12, Tom HM Ottenhoff11 and Mark Seielstad113

Author Affiliations

1 Human Genetics, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672

2 Infectious Disease, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672

3 Dept. of Internal Medicine, Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia

4 Health Research Unit, Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia

5 Dept. of Biochemistry, Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia

6 Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, Indonesia 10430

7 Infectious Disease Working Group, Medical Faculty, University of Indonesia, Jakarta, Indonesia

8 Samara Oblast Tuberculosis Dispensary, Samara City, Samara, Russian Federation

9 Clinical TB and HIV Group and Health Protection Agency, National Mycobacterium Reference Laboratory, The Blizard Institute, Barts and the London School of Medicine, Queen Mary College, University of London, London, UK

10 Department of Medicine, University of Cambridge, Cambridge, UK

11 Dept of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

12 Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

13 Institute for Human Genetics, University of California, San Francisco, California 94143-0794, USA, and Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, California 94118, USA

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BMC Medical Genetics 2012, 13:5  doi:10.1186/1471-2350-13-5

Published: 13 January 2012



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.


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.


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.


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.