Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight.
- Author:
Mi Hyun PARK
1
;
Soo Heon KWAK
;
Kwang Joong KIM
;
Min Jin GO
;
Hye Ja LEE
;
Kyung Seon KIM
;
Joo Yeon HWANG
;
Kuchan KIMM
;
Young Min CHO
;
Hong Kyu LEE
;
Kyong Soo PARK
;
Jong Young LEE
Author Information
1. Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Korea. leejy63@nih.go.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
affected sibpairs;
association;
linkage;
obesity;
overweight;
type 2 diabetes
- MeSH:
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
- From:Experimental & Molecular Medicine
2013;45(2):e7-
- CountryRepublic of Korea
- Language:English
-
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.
