J Korean Med Sci.  2013 Mar;28(3):415-423. 10.3346/jkms.2013.28.3.415.

Combined Genome-Wide Linkage and Association Analyses of Fasting Glucose Level in Healthy Twins and Families of Korea

Affiliations
  • 1Institute of Clinical Research, Inha University School of Medicine, Incheon, Korea.
  • 2Department of Biostatistics, University of Pittsburg, PA, USA.
  • 3Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea. namms@inha.ac.kr
  • 4Clinical Trial Center, Inha University Hospital, Incheon, Korea.
  • 5National Health Insurance Corporation, Seoul, Korea.
  • 6Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • 7Department of Epidemiology and Institute of Environment and Health, Seoul National University School of Public Health, Seoul, Korea.

Abstract

This study was undertaken to identify genetic polymorphisms that are associated with the risk of an elevated fasting glucose (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 monozygotic 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 single-nucleotide polymorphism (rs6138953) on the PTPRA gene in the 20p13 region (combined P = 1.8 x 10(-6)) was found to be associated with FG level, and the PRKCB1 gene (in 16p12.1) to be possibly associated with FG level. In conclusion, multiple regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2 are associated with FG level in our Korean twin-family cohort. The combined approach of genome-wide linkage and family-based association analysis is useful to identify novel or known genetic regions concerning FG level in a family cohort study.

Keyword

Fasting Glucose Level; Genome-Wide; Genetic Linkage; PRKCB1; PTPRA

MeSH Terms

Adult
Aged
Asian Continental Ancestry Group/*genetics
Blood Glucose/*genetics
Chromosomes, Human, Pair 15/genetics
Chromosomes, Human, Pair 16/genetics
Chromosomes, Human, Pair 2/genetics
Chromosomes, Human, Pair 20/genetics
Cohort Studies
Family
Female
*Genetic Linkage
*Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Protein Kinase C/genetics
Quantitative Trait Loci
Receptor-Like Protein Tyrosine Phosphatases, Class 4/*genetics
Republic of Korea
Twins, Monozygotic/*genetics
Blood Glucose
Protein Kinase C
Receptor-Like Protein Tyrosine Phosphatases, Class 4

Figure

  • Fig. 1 Genome-wide linkage analysis with the FG level.


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