Targeted ultra-deep sequencing of a South African Bantu-speaking cohort to comprehensively map and characterize common and novel variants in 65 pharmacologically-related genes

Pharmacogenet Genomics. 2019 Sep;29(7):167-178. doi: 10.1097/FPC.0000000000000380.


Background: African populations are characterised by high genetic diversity, which provides opportunities for discovering and elucidating novel variants of clinical importance, especially those affecting therapeutic outcome. Significantly more knowledge is however needed before such populations can take full advantage of the advances in precision medicine. Coupled with the need to concisely map and better understand the pharmacological implications of genetic diversity in populations of sub-Sharan African ancestry, the aim of this study was to identify and characterize known and novel variants present within 65 important absorption, distribution, metabolism and excretion genes.

Patients and methods: Targeted ultra-deep next-generation sequencing was used to screen a cohort of 40 South African individuals of Bantu ancestry.

Results: We identified a total of 1662 variants of which 129 are novel. Moreover, out of the 1662 variants 22 represent potential loss-of-function variants. A high level of allele frequency differentiation was observed for variants identified in this study when compared with other populations. Notably, on the basis of prior studies, many appear to be pharmacologically important in the pharmacokinetics of a broad range of drugs, including antiretrovirals, chemotherapeutic drugs, antiepileptics, antidepressants, and anticoagulants. An in-depth analysis was undertaken to interrogate the pharmacogenetic implications of this genetic diversity.

Conclusion: Despite the new insights gained from this study, the work illustrates that a more comprehensive understanding of population-specific differences is needed to facilitate the development of pharmacogenetic-based interventions for optimal drug therapy in patients of African ancestry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosome Mapping
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Variation
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Male
  • Pharmacogenomic Variants*
  • Sequence Analysis, DNA / methods*
  • South Africa / ethnology