After imputation of data from the 1000 Genomes Project into a genome-wide dataset of Ghanaian individuals with tuberculosis and controls, we identified a resistance locus on chromosome 11p13 downstream of the WT1 gene (encoding Wilms tumor 1). The strongest signal was obtained at the rs2057178 SNP (P = 2.63 × 10−9). Replication in Gambian, Indonesian and Russian tuberculosis case-control study cohorts increased the significance level for the association with this SNP to P = 2.57 × 10−11.
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Möller, M. & Hoal, E.G. Tuberculosis (Edinb.) 90, 71–83 (2010).
Vannberg, F.O., Chapman, S.J. & Hill, A.V. Immunol. Rev. 240, 105–116 (2011).
Intemann, C.D. et al. PLoS Pathog. 5, e1000577 (2009).
Thye, T. et al. Nat. Genet. 42, 739–741 (2010).
Li, Y., Willer, C.J., Ding, J., Scheet, P. & Abecasis, G.R. Genet. Epidemiol. 34, 816–834 (2010).
Huang, L. et al. Am. J. Hum. Genet. 84, 235–250 (2009).
Huff, V. Nat. Rev. Cancer 11, 111–121 (2011).
Maurer, U. et al. J. Biol. Chem. 276, 3727–3732 (2001).
Sciesielski, L.K., Kirschner, K.M., Scholz, H. & Persson, A.B. FEBS Lett. 584, 4665–4671 (2010).
Flynn, J.L. & Chan, J. Annu. Rev. Immunol. 19, 93–129 (2001).
Ottenhoff, T.H., Verreck, F.A. & Hoeve, M. Tuberculosis (Edinb.) 85, 53–64 (2005).
Ghana. The participation of affected individuals and the volunteers who served as controls is gratefully acknowledged, as are the contributions of field workers, nurses and physicians involved in the recruitment of participants, the staff of the Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR) and the excellent assistance of E. Abbeyquaye and L. Gankpala. The study protocol was approved by the Committee on Human Research, Publications and Ethics, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, and the Ethics Committee of the Ghana Health Service. Consent was obtained from the enrolled individuals or from their parents or guardians by signature or by thumbprint in case of illiteracy. This work was supported by the German Federal Ministry of Education and Research (BMBF), the TB or not TB Project, the German National Genome Research Network (NGFN1, 01GS0162; NGFN2, NIE-S17T20; and NGFN-PLUS, 01GS0811), the European Union Framework Programme 7 (201483; TB-EUROGEN) and the BMBF Tuberculosis Research Network (01KI0780).
The Gambia. We thank other members of the Wellcome Trust Case Control Consortium and collaborators for previous work on the Gambian sample sets. All samples were obtained with informed consent. Ethical approval for the study was granted by the Gambian MRC and the Gambian government joint ethical committee. Sample collection was supported by the Gambian MRC Unit funding, European Commission framework Programme awards, an MRC award (G0000690 to G.S.) and Wellcome Trust fellowship support (to A.V.S.H.). Laboratory work in Oxford was supported by the Wellcome Trust.
Indonesia. Written informed consent was obtained from all subjects, and the study was approved by the ethical committees of the Eijkman Institute of Molecular Biology and the Faculty of Medicine, Padjadjaran University, Hasan Sadikin Hospital. We gratefully acknowledge S. Marzuki, R.H.H. Nelwan and J.W.M. van der Meer for their continued support of the study. This study was supported by the Royal Netherlands Academy of Arts and Sciences (KNAW; KNAW99MED01), the Netherlands Organization for Scientific Research–Netherlands Foundation for the Advancement of Tropical Research (NWO-WOTRO) (Poverty Related Infection Oriented Research (PRIOR)-project) and the European Commission (QLK2-CT-2003-503367).
Russia. The participation of affected individuals and volunteer, control individuals is gratefully acknowledged. The study was approved by the Human Biology Research Ethics Committees of the University of Cambridge and Queen Mary College, and the local ethics committees in St. Petersburg and Samara, Russia. All participants provided written informed consent before being enrolled in the study. We thank O. Ignatyeva, I. Kontsevaya, S. Mironova, I. Fedorin and N. Malomanova for the recruitment of subjects and controls, as well as E. Stebbings, L. Kopanitsa and A. Speirs for DNA preparation. During the course of this study, S.N. was a Royal Society University Research Fellow and now holds the Wellcome Trust Senior Research Fellowship in Basic Biomedical Science. This study was supported by grants from the European Union Framework Programme 7 (201483; TB-EUROGEN), the Royal Society (RG090638), the Wellcome Trust (088838/Z/09/Z) and the European Research Council (ERC; starting grant 260477).
The authors declare no competing financial interests.
About this article
Association of human leukocyte antigens‐DQB2/DPA1/DPB1 polymorphism and pulmonary tuberculosis in the Chinese Uygur population
Molecular Genetics & Genomic Medicine (2019)
A Sex-Stratified Genome-Wide Association Study of Tuberculosis Using a Multi-Ethnic Genotyping Array
Frontiers in Genetics (2019)
An exome wide association study of pulmonary tuberculosis patients and their asymptomatic household contacts
Infection, Genetics and Evolution (2019)
Fine-mapping analysis of a chromosome 2 region linked to resistance to Mycobacterium tuberculosis infection in Uganda reveals potential regulatory variants
Genes & Immunity (2019)
Frontiers in Genetics (2019)