Tinashe Chikowore1, Tertia van Zyl2, Edith J M Feskens3, Karin R Conradie2. 1. Centre for Excellence in Nutrition, North-West University, Potchefstroom, North West Province 2520, South Africa. Electronic address: tinashedoc@gmail.com. 2. Centre for Excellence in Nutrition, North-West University, Potchefstroom, North West Province 2520, South Africa. 3. Wageningen University, Division of Human Nutrition, P.O. Box 17, 6700 AA Wageningen, The Netherlands.
Abstract
AIMS: 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. METHOD: 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.
AIMS: 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. METHOD: 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: América Liliana Miranda-Lora; Jenny Vilchis-Gil; Daniel B Juárez-Comboni; Miguel Cruz; Miguel Klünder-Klünder Journal: Front Endocrinol (Lausanne) Date: 2021-03-12 Impact factor: 5.555