Using multi-way admixture mapping to elucidate TB susceptibility in the South African Coloured population

BMC Genomics

Eileen G Hoal¹  Marlo Möller¹  Paul D van Helden¹  Christopher R Gignoux²  Lize van der Merwe¹  Michelle Daya¹ 

[1] Molecular Biology and Human Genetics, MRC Centre for TB Research and the DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa;Department of Genetics, Stanford University, Stanford, California, USA

关键词: B7-H5;    OSM;    GADD45A;    17q22;    15q15;    Local ancestry inference;   

Others  :  1091088
DOI  :  10.1186/1471-2164-15-1021

 received in 2014-07-07, accepted in 2014-11-19,  发布年份 2014

【 摘 要 】

Background

The admixed South African Coloured population is ideally suited to the discovery of tuberculosis susceptibility genetic variants and their probable ethnic origins, but previous attempts at finding such variants using genome-wide admixture mapping were hampered by the inaccuracy of local ancestry inference. In this study, we infer local ancestry using the novel algorithm implemented in RFMix, with the emphasis on identifying regions of excess San or Bantu ancestry, which we hypothesize may harbour TB susceptibility genes.

Results

Using simulated data, we demonstrate reasonable accuracy of local ancestry inference by RFMix, with a tendency towards miss-calling San ancestry as Bantu. Regions with either excess San ancestry or excess African (San or Bantu) ancestry are less likely to be affected by this bias, and we therefore proceeded to identify such regions, found in cases but not in controls (642 cases and 91 controls). A number of promising regions were found (overall p-values of 7.19×10^-5 for San ancestry and <2.00×10^-16 for African ancestry), including chromosomes 15q15 and 17q22, which are close to genomic regions previously implicated in TB. Promising immune-related susceptibility genes such as the GADD45A, OSM and B7-H5 genes are also harboured in the identified regions.

Conclusion

Admixture mapping is feasible in the South African Coloured population and a number of novel TB susceptibility genomic regions were uncovered.

【 授权许可】

   
2014 Daya et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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