The role of ancestry in TB susceptibility of an admixed South African population. Daya, M.; van der Merwe, L.; van Helden, P. D.; Möller, M.; and Hoal, E. G. Tuberculosis (Edinburgh, Scotland), 94(4):413--420, July, 2014. 00002
doi  abstract   bibtex   
Genetic susceptibility to tuberculosis (TB) has been well established and this, taken together with variation in susceptibility observed between different geographic and ethnic populations, implies that susceptibility to TB may in part be affected by ethnicity. In a previous genome-wide TB case-control study (642 cases and 91 controls) of the admixed South African Coloured (SAC) population, we found a positive correlation between African San ancestry and TB susceptibility, and negative correlations with European and Asian ancestries. Since genome-wide data was available for only a small number of controls in the previous study, we endeavored to validate this finding by genotyping a panel of ancestry informative markers (AIMs) in additional individuals, yielding a data set of 918 cases and 507 controls. Ancestry proportions were estimated using the AIMs for each of the source populations of the SAC (African San, African non-San, European, South Asian and East Asian). Using logistic regression models to test for association between TB and ancestry, we confirmed the substantial effect of ancestry on TB susceptibility. We also investigated the effect of adjusting for ancestry in candidate gene TB association studies of the SAC. We report a polymorphism that is no longer significantly associated with TB after adjustment for ancestry, a polymorphism that is significantly associated with TB only after adjustment for ancestry, and a polymorphism where the association significance remains unchanged. By comparing the allele frequencies of these polymorphisms in the source populations of the SAC, we demonstrate that association results are likely to be affected by adjustment for ancestry if allele frequencies differ markedly in the source populations of the SAC.
@article{ daya_role_2014,
  title = {The role of ancestry in {TB} susceptibility of an admixed {South} {African} population},
  volume = {94},
  issn = {1873-281X},
  doi = {10.1016/j.tube.2014.03.012},
  abstract = {Genetic susceptibility to tuberculosis (TB) has been well established and this, taken together with variation in susceptibility observed between different geographic and ethnic populations, implies that susceptibility to TB may in part be affected by ethnicity. In a previous genome-wide TB case-control study (642 cases and 91 controls) of the admixed South African Coloured (SAC) population, we found a positive correlation between African San ancestry and TB susceptibility, and negative correlations with European and Asian ancestries. Since genome-wide data was available for only a small number of controls in the previous study, we endeavored to validate this finding by genotyping a panel of ancestry informative markers (AIMs) in additional individuals, yielding a data set of 918 cases and 507 controls. Ancestry proportions were estimated using the AIMs for each of the source populations of the SAC (African San, African non-San, European, South Asian and East Asian). Using logistic regression models to test for association between TB and ancestry, we confirmed the substantial effect of ancestry on TB susceptibility. We also investigated the effect of adjusting for ancestry in candidate gene TB association studies of the SAC. We report a polymorphism that is no longer significantly associated with TB after adjustment for ancestry, a polymorphism that is significantly associated with TB only after adjustment for ancestry, and a polymorphism where the association significance remains unchanged. By comparing the allele frequencies of these polymorphisms in the source populations of the SAC, we demonstrate that association results are likely to be affected by adjustment for ancestry if allele frequencies differ markedly in the source populations of the SAC.},
  language = {eng},
  number = {4},
  journal = {Tuberculosis (Edinburgh, Scotland)},
  author = {Daya, Michelle and van der Merwe, Lize and van Helden, Paul D. and Möller, Marlo and Hoal, Eileen G.},
  month = {July},
  year = {2014},
  pmid = {24832562},
  note = {00002 },
  keywords = {Adult, African Continental Ancestry Group, Asian Continental Ancestry Group, Case-Control Studies, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, South Africa, Tuberculosis, Young Adult},
  pages = {413--420}
}
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