title: Genetic diversity of variants involved in drug response and metabolism in Sri Lankan populations: implications for clinical implementation of pharmacogenomics.
abstract: BACKGROUND
  Interpopulation differences in drug responses are well documented, and in some cases they correspond to differences in the frequency of associated genetic markers. Understanding the diversity of genetic markers associated with drug response across different global populations is essential to infer population rates of drug response or risk for adverse drug reactions, and to guide implementation of pharmacogenomic testing. Sri Lanka is a culturally and linguistically diverse nation, but little is known about the population genetics of the major Sri Lankan ethnic groups. The objective of this study was to investigate the diversity of pharmacogenomic variants in the major Sri Lankan ethnic groups.
  
  
  METHODS
  We examined the allelic diversity of more than 7000 variants in genes involved in drug biotransformation and response in the three major ethnic populations of Sri Lanka (Sinhalese, Sri Lankan Tamils, and Moors), and compared them with other South Asian, South East Asian, and European populations using Wright's Fixation Index, principal component analysis, and STRUCTURE analysis.
  
  
  RESULTS
  We observed overall high levels of similarity within the Sri Lankan populations (median FST=0.0034), and between Sri Lankan and other South Asian populations (median FST=0.0064). Notably, we observed substantial differentiation between Sri Lankan and European populations for important pharmacogenomic variants related to warfarin (VKORC1 rs9923231) and clopidogrel (CYP2C19 rs4986893) response.
  
  
  CONCLUSIONS
  These data expand our understanding of the population structure of Sri Lanka, provide a resource for pharmacogenomic research, and have implications for the clinical use of genetic testing of pharmacogenomic variants in these populations.
authors.affiliation: aTranslational Laboratory in Genetic Medicine, Agency for Science, Technology, and Research bSaw Swee Hock School of Public Health cNUS Graduate School for Integrative Sciences and Engineering dLife Sciences Institute Departments of eStatistics and Applied Probability fMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Departments of gParasitology hAnatomy, University of Colombo, Colombo, Sri Lanka iDepartment of Pediatrics, Division of Translational Therapeutics jCentre for Molecular Medicine and Therapeutics, Child and Family Research Institute kDepartment of Medicine, Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sze Ling
authors.initials: SL
authors.lastname: Chan
authors.forename: Nilakshi
authors.initials: N
authors.lastname: Samaranayake
authors.forename: Colin J D
authors.initials: CJ
authors.lastname: Ross
authors.forename: Meng Tiak
authors.initials: MT
authors.lastname: Toh
authors.forename: Bruce
authors.initials: B
authors.lastname: Carleton
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Yik Ying
authors.initials: YY
authors.lastname: Teo
authors.forename: Vajira H W
authors.initials: VH
authors.lastname: Dissanayake
authors.forename: Liam R
authors.initials: LR
authors.lastname: Brunham
mesh_terms: D000077144:Clopidogrel; D005006:Ethnicity / Q000235:genetics*; D005819:Genetic Markers / Q000187:drug effects*; D014644:Genetic Variation / Q000187:drug effects*; D005828:Genetics, Population; D006801:Humans; D010597:Pharmacogenetics; D025341:Principal Component Analysis; D013188:Sri Lanka / Q000208:ethnology; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014859:Warfarin / Q000494:pharmacology
chemical_list: D005819:Genetic Markers; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine