Abstract

In 1994, it was estimated that more than 13 million Americans suffered from diabetes mellitus, with approximately 95% having non- insulin-dependent diabetes mellitus (NIDDM). Diabetes is the leading cause of blindness and non-trauma related amputations in the United States and is a risk factor for other disorders such as hypertension and cardiovascular disease, resulting in significant morbidity and mortality. The specific hypothesis of this proposal is that there exists a set of mappable genes that predispose to the development of NIDDM and identification of the disease genes should be possible through positional cloning using an affected sib-pair strategy. To test this hypothesis, it is proposed that statistical genetic analysis be performed on phenotypic and genotypic data collected from the 500 sib-pair families of the Finland-United States Investigation of NIDDM Genetics (FUSION), a multicenter study aimed at identifying genes for NIDDM.
The specific aims of this proposal are: 1. Perform segregation analysis of NIDDM-related quantitative traits. Traditional NIDDM-related quantitative traits will be tested along with alternative traits which may have greater discriminatory power. 2. Perform linkage analysis. These analyses will include risk- ratio-based linkage analysis, mode-of-inheritance-based linkage analysis, and. linkage analysis of NIDDM-related quantitative traits.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK009525-02
Application #
2656056
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Hyde, James F
Project Start
1997-09-01
Project End
Budget Start
1997-09-01
Budget End
1998-06-30
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Silander, Kaisa; Scott, Laura J; Valle, Timo T et al. (2004) A large set of Finnish affected sibling pair families with type 2 diabetes suggests susceptibility loci on chromosomes 6, 11, and 14. Diabetes 53:821-9
Hauser, Elizabeth R; Watanabe, Richard M; Duren, William L et al. (2004) Ordered subset analysis in genetic linkage mapping of complex traits. Genet Epidemiol 27:53-63
Fingerlin, Tasha E; Erdos, Michael R; Watanabe, Richard M et al. (2002) Variation in three single nucleotide polymorphisms in the calpain-10 gene not associated with type 2 diabetes in a large Finnish cohort. Diabetes 51:1644-8
Avogaro, Angelo; Watanabe, Richard M; Gottardo, Lucia et al. (2002) Glucose tolerance during moderate alcohol intake: insights on insulin action from glucose/lactate dynamics. J Clin Endocrinol Metab 87:1233-8
Douglas, J A; Erdos, M R; Watanabe, R M et al. (2001) The peroxisome proliferator-activated receptor-gamma2 Pro12A1a variant: association with type 2 diabetes and trait differences. Diabetes 50:886-90
Mohlke, K L; Lange, E M; Valle, T T et al. (2001) Linkage disequilibrium between microsatellite markers extends beyond 1 cM on chromosome 20 in Finns. Genome Res 11:1221-6
Ghosh, S; Watanabe, R M; Valle, T T et al. (2000) The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. I. An autosomal genome scan for genes that predispose to type 2 diabetes. Am J Hum Genet 67:1174-85
Ghosh, S; Watanabe, R M; Hauser, E R et al. (1999) Type 2 diabetes: evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs. Proc Natl Acad Sci U S A 96:2198-203
Ghosh, S; Langefeld, C D; Ally, D et al. (1999) The W64R variant of the beta3-adrenergic receptor is not associated with type II diabetes or obesity in a large Finnish sample. Diabetologia 42:238-44
Watanabe, R M; Steil, G M; Bergman, R N (1998) Critical evaluation of the combined model approach for estimation of prehepatic insulin secretion. Am J Physiol 274:E172-83

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