Exp Mol Med.
2013 Feb;45(2):e7.
Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight
- Affiliations
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- 1Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Korea. leejy63@nih.go.kr
- 2Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Korea.
- 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. kspark@snu.ac.kr
- 4WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, Korea.
Abstract
- The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. Identification of genetic determinants for complex diseases, such as type 2 diabetes, may provide insight into disease pathogenesis. The aim of the study was to investigate the shared genetic factors that predispose individuals to being overweight and developing type 2 diabetes. We conducted genome-wide linkage analyses for type 2 diabetes in 386 affected individuals (269 sibpairs) from 171 Korean families and association analyses with single-nucleotide polymorphisms of candidate genes within linkage regions to identify genetic variants that predispose individuals to being overweight and developing type 2 diabetes. Through fine-mapping analysis of chromosome 4q34-35, we detected a locus potentially linked (nonparametric linkage 2.81, logarithm of odds 2.27, P=6 x 10-4) to type 2 diabetes in overweight or obese individuals (body mass index, BMI> or =23 kg m-2). Multiple regression analysis with type 2 diabetes-related phenotypes revealed a significant association (false discovery rate (FDR) P=0.006 for rs13144140; FDR P=0.002 for rs6830266) between GPM6A (rs13144140) and BMI and waist-hip ratio, and between NEIL3 (rs6830266) and insulin level from 1314 normal individuals. Our systematic search of genome-wide linkage and association studies, demonstrate that a linkage peak for type 2 diabetes on chromosome 4q34-35 contains two type 2 diabetes-related genes, GPM6A and NEIL3.
Keyword
MeSH Terms
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Body Mass Index
Chromosomes, Human, Pair 4/*genetics
Diabetes Mellitus, Type 2/*complications/*genetics
Female
Genetic Linkage
*Genetic Loci
*Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Middle Aged
Overweight/*complications/*genetics
Phenotype
Physical Chromosome Mapping
Statistics, Nonparametric
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