title: Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight.
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.
authors: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Korea.
authors: Mi-Hyun
authors: MH
authors: Park
authors: Soo Heon
authors: SH
authors: Kwak
authors: Kwang Joong
authors: KJ
authors: Kim
authors: Min Jin
authors: MJ
authors: Go
authors: Hye-Ja
authors: HJ
authors: Lee
authors: Kyung-Seon
authors: KS
authors: Kim
authors: Joo-Yeon
authors: JY
authors: Hwang
authors: Kuchan
authors: K
authors: Kimm
authors: Young-Min
authors: YM
authors: Cho
authors: Hong Kyu
authors: HK
authors: Lee
authors: Kyong Soo
authors: KS
authors: Park
authors: Jong-Young
authors: JY
authors: Lee
mesh_terms: D015992:Body Mass Index; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications* / Q000235:genetics*; D010641:Phenotype; D020161:Physical Chromosome Mapping; D018709:Statistics, Nonparametric
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