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• W2076363277 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 × 10−4) to type 2 diabetes in overweight or obese individuals (body mass index, BMI⩾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. The genes GPM6A and NEIL3 predispose people to obesity and type-2 diabetes (T2D), a genome-wide linkage analysis of Korean individuals has shown. The study, led by Jong-Young Lee of the National Institute of Health, Korea, adds to the list of almost 25 genes previously linked to increased risk for T2D, which were identified in earlier genome-wide association studies. Obesity is the most important determinant of the onset of T2D, but environmental and genetic factors contribute to the onset of both conditions. Further research is needed to establish exactly how variants of the two newly discovered genetic culprits predispose people to metabolic dysfunction, and whether these variants are found in non-Korean populations. The relative homogeneity of the Korean population might explain why earlier studies failed to identify the two new genes responsible for T2D." @default.
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• W2076363277 date "2013-02-08" @default.
• W2076363277 modified "2023-10-16" @default.
• W2076363277 title "Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight" @default.
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• W2076363277 doi "https://doi.org/10.1038/emm.2013.5" @default.
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