Combined genome-wide linkage and association analyses of fasting glucose level in healthy twins and families of Korea

초록

Type 2 diabetes is a major chronic disease with high consistence in monozygotic (MZ) twins. Fasting glucose (FG) level is one of the traits related to type 2 diabetes. This study was undertaken to identify genetic polymorphisms that are associated with the risk of an elevated FG level using genome-wide analyses. We explored a quantitative trait locus (QTL) for FG level in a genome-wide study from a Korean twin-family cohort (the Healthy Twin Study) using a combined linkage and family-based association analysis approach. We investigated 1,754 individuals, which included 432 families and 219 pairs of MZ twins. Regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2, were found to show evidence of linkage with FG level, and several markers in these regions were found to be significantly associated with FG level using family-based or general association tests. In particular, a SNP (rs6138953) on the PTPRA gene in the 20p13 region (combined p=1.8ⅹ10-6) was found to be significantly associated with FG level, and the PRKCB1 gene (in 16p12.1) to be possibly associated with FG level. In addition, it was found that PTPRA (or PRKCB1) and several novel genes have epistatic effects on a risk of an elevated FG level. We found multiple regions that showed evidence of linkage and an association with FG level in our Korean twin-family cohort. The findings of this study increase understanding of the pathogenesis of type 2 diabetes in the Korean population.