title: Genetic-risk assessment of GWAS-derived susceptibility loci for type 2 diabetes in a 10 year follow-up of a population-based cohort study.
abstract: To date, genome-wide meta-analyses have identified genetic susceptibility to type 2 diabetes mellitus (T2D) predominantly in populations of European ancestry. However, comprehensive genetic-risk assessment based on previous GWAS loci has not been fully tested in non-European populations. To evaluate whether a genetic-risk score (GRS) could improve T2D-risk prediction in the Korean population, a GRS (GRS-55) was constructed by summing 55 risk alleles based on the 1000 Genomes imputation in the Korean Association Resource study (T2D cases=1042 and controls=2943 at baseline). We also constructed another GRS (GRS-19) based on nominal significance and consistent direction of effect. In mean difference tests, the mean value of the GRS-19 was significantly higher in T2D cases than in controls at baseline examination. In a model adjusted for area, age, sex and body mass index, weighted GRS-19 was found to be associated with enhanced effect sizes of T2D risk under consistent C-statistics. In addition, we confirmed cumulative risk effects on incidence rates of T2D, fasting plasma glucose and glycated hemoglobin (HbA1c) levels in a longitudinal 10 year of follow-up study. These findings highlight that a genotype score comprised of 19 common variants contributed to T2D-risk prediction in the Korean population. Further multi-locus epistatic interactions may provide the possibility to improve risk prediction in C-statistics for discrimination or reclassification.
authors.affiliation: Division of Structural and Functional Genomics, The Center for Genome Science, Korea National Institute of Health, KCDC, Osong, Republic of Korea.
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Go
authors.affiliation: Division of Structural and Functional Genomics, The Center for Genome Science, Korea National Institute of Health, KCDC, Osong, Republic of Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Division of Structural and Functional Genomics, The Center for Genome Science, Korea National Institute of Health, KCDC, Osong, Republic of Korea.|Department of Biostatistics, Soonchunhyang University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Suyeon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Soo Heon
authors.initials: SH
authors.lastname: Kwak
authors.affiliation: Division of Structural and Functional Genomics, The Center for Genome Science, Korea National Institute of Health, KCDC, Osong, Republic of Korea.
authors.forename: Bong-Jo
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Division of Structural and Functional Genomics, The Center for Genome Science, Korea National Institute of Health, KCDC, Osong, Republic of Korea.
authors.forename: Juyoung
authors.initials: J
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015415:Biomarkers; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D040641:Quantitative Trait Loci; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers