The transmission of complex phenotypes such as type 2 diabetes is likely to reflect the actions and interactions of multiple genetic and environmental factors. Linkage studies designed to localize genes for type 2 diabetes have yield few regions with highly significant evidence for linkage and fewer still that have been replicated in additional studies. While these results are disappointing, they can hardly be considered surprising. The failure of the current generation of studies to demonstrate conclusive and reproducible localization of the genes contributing to type 2 diabetes likely results from the combined effects of inadequate sample sizes, incorrect or incomplete models for genetic analysis, and the genuine complexity of the genetic component to disease susceptibility. While it is widely recognized that increasing the size of the sample included in linkage studies will provide the power to detect and localize susceptibility loci with modesty or moderate effects, collection of family data is the most expensive and time-consuming aspect of linkage studies. In an effort to maximize the utility of data that already have been collected to map genes for type 2 diabetes, we have formed The International Type 2 Diabetes Linkage Analysis Consortium to combine existing data sets for linkage analysis.
The specific aims are: (1) to conduct linkage analyses over all human autosomes and the X chromosome within and across the racial/ethnic groups represented in the combined Consortium data to identify regions most likely to contain type 2 diabetes susceptibility loci; and (2) to conduct additional genotyping in Consortium data in regions of interest identified in analyses of Consortium data and for mutations in diabetes susceptibility loci identified by us or others during the course of this study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DK058026-05S2
Application #
6952952
Study Section
Genome Study Section (GNM)
Program Officer
Mckeon, Catherine T
Project Start
1999-08-01
Project End
2007-01-31
Budget Start
2003-08-18
Budget End
2007-01-31
Support Year
5
Fiscal Year
2004
Total Cost
$1,162,306
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Qin, Wen; Zhang, Rong; Hu, Cheng et al. (2010) A variation in NOS1AP gene is associated with repaglinide efficacy on insulin resistance in type 2 diabetes of Chinese. Acta Pharmacol Sin 31:450-4
Ng, M C Y; Lam, V K L; Tam, C H T et al. (2010) Association of the POU class 2 homeobox 1 gene (POU2F1) with susceptibility to Type 2 diabetes in Chinese populations. Diabet Med 27:1443-9
Lu, J; Hu, C; Hu, W et al. (2010) A common variant of NOS1AP is associated with QT interval duration in a Chinese population with Type 2 diabetes. Diabet Med 27:1074-9
Prokopenko, Inga; Zeggini, Eleftheria; Hanson, Robert L et al. (2009) Linkage disequilibrium mapping of the replicated type 2 diabetes linkage signal on chromosome 1q. Diabetes 58:1704-9
Guan, Weihua; Pluzhnikov, Anna; Cox, Nancy J et al. (2008) Meta-analysis of 23 type 2 diabetes linkage studies from the International Type 2 Diabetes Linkage Analysis Consortium. Hum Hered 66:35-49
Hu, Cheng; Jia, Weiping; Zhang, Weihua et al. (2008) An evaluation of the performance of HapMap SNP data in a Shanghai Chinese population: analyses of allele frequency, linkage disequilibrium pattern and tagging SNPs transferability on chromosome 1q21-q25. BMC Genet 9:19
Roberts, Caroline G P; Shen, Haiqing; Mitchell, Braxton D et al. (2007) Variants in scavenger receptor class B type I gene are associated with HDL cholesterol levels in younger women. Hum Hered 64:107-13
McArdle, Patrick F; Dytch, Harvey; O'Connell, Jeffery R et al. (2007) Homozygosity by descent mapping of blood pressure in the Old Order Amish: evidence for sex specific genetic architecture. BMC Genet 8:66
Hsueh, Wen-Chi; Silver, Kristi D; Pollin, Toni I et al. (2007) A genome-wide linkage scan of insulin level derived traits: the Amish Family Diabetes Study. Diabetes 56:2643-8
Wittke-Thompson, Jacqueline K; Ambrose, Nicoline; Yairi, Ehud et al. (2007) Genetic studies of stuttering in a founder population. J Fluency Disord 32:33-50

Showing the most recent 10 out of 35 publications