title: Predictive utility of a genetic risk score of common variants associated with type 2 diabetes in a black South African population.
abstract: OBJECTIVE
  To determine the predictive utility of polygenic risk scores of common variants associated with type 2 diabetes derived from the European and Asian ethnicities among a black South African population.
  
  
  METHODS
  Our study was a case-control study nested within the Prospective Urban and Rural Epidemiological (PURE) study of 178 male and female cases, matched for age and gender with 178 controls. Four types of genetic risk scores (GRS) were developed from 66 selected SNPs. These comprised of beta cell related variants (GRSb), variants which had significant associations with T2D in our study (GRSn), variants from the trans-ethnic meta-analysis (GRStrans) and all the 66 selected SNPs (GRSt).
  
  
  RESULTS
  Of the GRS's, only GRSn was associated with increased risk of T2D as indicated by an OR (95CI) of 1.21 (1.02-1.43) p-value=0.015. Stratified analysis of age and BMI, indicated the GRSn to be significantly associated with T2D among the non-obese and participants less than 50years. The area under the ROC of the T2D risk factors only was 0.652 (p value<0.001) and with the addition of GRSn it was 0.665 (p value<0.001).
  
  
  CONCLUSIONS
  The GRS of European and Asian derived variants have limited clinical utility in the black South African population. The inclusion of population specific variants in the GRS is pivotal.
authors.affiliation: Centre for Excellence in Nutrition, North-West University, Potchefstroom, North West Province 2520, South Africa. Electronic address: tinashedoc@gmail.com.
authors.forename: Tinashe
authors.initials: T
authors.lastname: Chikowore
authors.affiliation: Centre for Excellence in Nutrition, North-West University, Potchefstroom, North West Province 2520, South Africa.
authors.forename: Tertia
authors.initials: T
authors.lastname: van Zyl
authors.affiliation: Wageningen University, Division of Human Nutrition, P.O. Box 17, 6700 AA Wageningen, The Netherlands.
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.affiliation: Centre for Excellence in Nutrition, North-West University, Potchefstroom, North West Province 2520, South Africa.
authors.forename: Karin R
authors.initials: KR
authors.lastname: Conradie
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D044383:Black People / Q000208:ethnology* / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D044465:White People / Q000208:ethnology / Q000235:genetics
keywords: BMI; Clinical use; GRS; Polygenic risk score