title: Clinical and pharmacogenomic implications of genetic variation in a Southern Ethiopian population.
abstract: Africa is home to genetically diverse human populations. We compared the genetic structure of the Wolaita ethnic population from Southern Ethiopia (WETH, n=120) with HapMap populations using genome-wide variants. We investigated allele frequencies of 443 clinically and pharmacogenomically relevant genetic variants in WETH compared with HapMap populations. We found that WETH were genetically most similar to the Kenya Maasai and least similar to the Japanese in HapMap. Variant alleles associated with increased risk of adverse reactions to drugs used for treating tuberculosis (rs1799929 and rs1495741 in NAT2), thromboembolism (rs7294, rs9923231 and rs9934438 in VKORC1), and HIV/AIDS and solid tumors (rs2242046 in SLC28A1) had significantly higher frequencies in WETH compared with African ancestry HapMap populations. Our results illustrate that clinically relevant pharmacogenomic loci display allele frequency differences among African populations. We conclude that drug dosage guidelines for important global health diseases should be validated in genetically diverse African populations.
authors: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Fasil
authors: F
authors: Tekola-Ayele
authors: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Adebowale
authors: A
authors: Adeyemo
authors: Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
authors: Abraham
authors: A
authors: Aseffa
authors: Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
authors: Elena
authors: E
authors: Hailu
authors: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors: Chris
authors: C
authors: Finan
authors: Brighton and Sussex Medical School, Falmer, Brighton, UK.
authors: Gail
authors: G
authors: Davey
authors: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Charles N
authors: CN
authors: Rotimi
authors: Brighton and Sussex Medical School, Falmer, Brighton, UK.
authors: Melanie J
authors: MJ
authors: Newport
mesh_terms: D044383:Black People / Q000208:ethnology* / Q000235:genetics*; D015331:Cohort Studies; D005002:Ethiopia / Q000208:ethnology; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011159:Population Surveillance / Q000379:methods