Abstract
We combined two tuberculosis genome-wide association studies from Ghana and The Gambia with subsequent replication in a combined 11,425 individuals. rs4331426, located in a gene-poor region on chromosome 18q11.2, was associated with disease (combined P = 6.8 × 10−9, odds ratio = 1.19, 95% CI = 1.13–1.27). Our study demonstrates that genome-wide association studies can identify new susceptibility loci for infectious diseases, even in African populations, in which levels of linkage disequilibrium are particularly low.
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Change history
07 November 2010
In the version of this article initially published, the order of the author list was incorrect. The two final authors should have been listed as the African TB Genetics Consortium and The Wellcome Trust Case Control Consortium. The error has been corrected in the HTML and PDF versions of the article.
22 September 2011
In the version of this article initially published, an acknowledgment was missing. The study was supported by funding from the NIHR Oxford Biomedical Research Centre programme. The error has been corrected in the HTML and PDF versions of the article.
References
The World Health Organization. Lancet 373, 1145 (2009).
The World Health Organization. Wkly. Epidemiol. Rec. 78, 122–128 (2003).
Comstock, G.W. Am. Rev. Respir. Dis. 117, 621–624 (1978).
Stead, W.W., Senner, J.W., Reddick, W.T. & Lofgren, J.P. N. Engl. J. Med. 322, 422–427 (1990).
WTCCC. Nature 447, 661–678 (2007).
Jallow, M. et al. Nat. Genet. 41, 657–665 (2009).
Fellay, J. et al. Science 317, 944–947 (2007).
Ziegler, A. Genet. Epidemiol. 33, S45–S50 (2009).
Gagneux, S. et al. Proc. Natl. Acad. Sci. USA 103, 2869–2873 (2006).
Fitness, J. et al. Am. J. Trop. Med. Hyg. 71, 341–349 (2004).
Lienhardt, C. et al. Am. J. Epidemiol. 155, 1066–1073 (2002).
Thye, T. et al. Hum. Mol. Genet. 18, 381–388 (2009).
Intemann, C.D. et al. PLoS Pathog. 5, e1000577 (2009).
Acknowledgements
We would like to thank the subjects and families, field workers, nurses and physicians who contributed to these studies. We thank M. McCarthy and C. Khor for critical assessment of the manuscript. The study was supported by funding from the NIHR Oxford Biomedical Research Centre programme.
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T.T., F.O.V., S.H.W., C.G.M., R.D.H. and A.V.S.H. wrote the paper. T.T., F.O.V. and S.H.W. performed the genotyping. T.T., F.O.V. and S.H.W. performed the analysis. T.T., F.O.V., S.H.M., Y.Y.T. and K.S. contributed to the statistical methods. E.O.-D. and J.G. led the sample procurement and supervision of field work in Kumasi and Accra, respectively. T.T., F.O.V., S.H.W., I.O., P.C.H., F.S.-J., A.E., M.A.C., S.F., D.K.W., L.S., S.M., A.C.C., B.N., K.R., D.K., P.E.F., G.S., M.N., C.L., R.A.A., T.C., A.Z., A.P.M., C.G.M., R.D.H. and A.V.S.H. contributed to the experimental design and collection of the sample cohorts. All authors critically reviewed the manuscript. T.T., F.O.V., C.G.M., R.D.H. and A.V.S.H. led the research effort.
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A full list of members is provided in the Supplementary Note.
A full list of members is provided in the Supplementary Note.
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Supplementary Note, Supplementary Figure 1, Supplementary Tables 1–5 and Supplementary Methods (PDF 1905 kb)
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Thye, T., Vannberg, F., Wong, S. et al. Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2. Nat Genet 42, 739–741 (2010). https://doi.org/10.1038/ng.639
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DOI: https://doi.org/10.1038/ng.639
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