Genome-Wide Search for Type 2 Diabetes/Impaired Glucose Homeostasis Susceptibility Genes in the Chinese
Significant Linkage to Chromosome 6q21-q23 and Chromosome 1q21-q24
- Kunsan Xiang12,
- Yanqing Wang1,
- Taishan Zheng1,
- Weiping Jia12,
- Jie Li1,
- Lei Chen12,
- Kunxue Shen1,
- Songhua Wu12,
- Xin Lin1,
- Guodong Zhang1,
- Congrong Wang2,
- Suijun Wang12,
- Huijuan Lu1,
- Qichen Fang1,
- Yi Shi1,
- Rong Zhang1,
- Jing Xu1 and
- Qin Weng1
- 1Shanghai Diabetes Institute, Shanghai Jiaotong University No. 6 People’s Hospital, Shanghai, China
- 2Department of Endocrinology and Metabolism, Shanghai Jiaotong University No. 6 People’s Hospital, Shanghai, China
- Address correspondence and reprint requests to Dr. Kunsan Xiang, Shanghai Diabetes Institute, Shanghai Jiaotong University No. 6 People’s Hospital, 600 Yishan Rd., Shanghai 200233, China. E-mail: sphxiang{at}public.sta.net.cn
Abstract
This genome-wide search for susceptibility genes to type 2 diabetes/impaired glucose homeostasis (IGH) was performed on a relatively homogenous Chinese sample with a total number of 257 pedigrees and 385 affected sibpairs. Two regions showed significant linkage to type 2 diabetes/IGH in the Chinese. The region showing linkage to type 2 diabetes/IGH from the entire sample group analysis was located on chromosome 6q21-q23 (128.93 cM, 1-LOD [logarithm of odds] support interval between 124 and 142 cM, according to the Marshfield genetic map), with a maximum likelihood score of 6.23, a nonparametric linkage (all) score of 4.48, and empirical P value <0.001. With a subanalysis based on 101 affected sibpairs with age at diagnosis of type 2 diabetes/IGH <40 years, we detected significant evidence for linkage to chromosome 1q21-q24 (192.1 cM, 1-LOD support interval between 182 and 197 cM), with a maximum likelihood score of 8.91, a nonparametric linkage (all) score of 5.70, and empirical P value <0.001. No interaction was observed between these two regions. Our independent replication of the region on chromosome 1q that has been shown to be linked significantly to type 2 diabetes/IGH in Chinese supports the notion that gene(s) in this region may be universally important in the development of human type 2 diabetes.
- ASP, affected sibpair
- IA-2, protein tyrosine phosphatase-like protein
- IGH, impaired glucose homeostasis
- LOD, logarithm of odds
- MLS, maximum likelihood score
- MODY, maturity-onset diabetes of the young
- NPL, nonparametric linkage
Footnotes
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Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.
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- Accepted October 15, 2003.
- Received May 30, 2003.
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