title: Utilizing Genetic Predisposition Score in Predicting Risk of Type 2 Diabetes Mellitus Incidence: A Community-based Cohort Study on Middle-aged Koreans.
abstract: Contribution of genetic predisposition to risk prediction of type 2 diabetes mellitus (T2DM) was investigated using a prospective study in middle-aged adults in Korea. From a community cohort of 6,257 subjects with 8 yr' follow-up, genetic predisposition score with subsets of 3, 18, 36 selected single nucleotide polymorphisms (SNPs) (genetic predisposition score; GPS-3, GPS-18, GPS-36) in association with T2DM were determined, and their effect was evaluated using risk prediction models. Rs5215, rs10811661, and rs2237892 were in significant association with T2DM, and hazard ratios per risk allele score increase were 1.11 (95% confidence intervals: 1.06-1.17), 1.09 (1.01-1.05), 1.04 (1.02-1.07) with GPS-3, GPS-18, GPS-36, respectively. Changes in AUC upon addition of GPS were significant in simple and clinical models, but the significance disappeared in full clinical models with glycated hemoglobin (HbA1c). For net reclassification index (NRI), significant improvement observed in simple (range 5.1%-8.6%) and clinical (3.1%-4.4%) models were no longer significant in the full models. Influence of genetic predisposition in prediction ability of T2DM incidence was no longer significant when HbA1c was added in the models, confirming HbA1c as a strong predictor for T2DM risk. Also, the significant SNPs verified in our subjects warrant further research, e.g. gene-environmental interaction and epigenetic studies.
authors.affiliation: Center for Clinical Preventive Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hye Yin
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea.
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea.
authors.forename: Yun-Chul
authors.initials: YC
authors.lastname: Hong
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D056910:Republic of Korea / Q000453:epidemiology; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity
keywords: Diabetes Mellitus; Genetic Predisposition; Hemoglobin A, Glycosylated