Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2000 Nov;67(5):1174-85.
Epub 2000 Oct 13.

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

S Ghosh  1 , R M Watanabe, T T Valle, E R Hauser, V L Magnuson, C D Langefeld, D S Ally, K L Mohlke, K Silander, K Kohtamäki, P Chines, J Balow Jr, G Birznieks, J Chang, W Eldridge, M R Erdos, Z E Karanjawala, J I Knapp, K Kudelko, C Martin, A Morales-Mena, A Musick, T Musick, C Pfahl, R Porter, J B Rayman
Affiliations
Multicenter Study

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

S Ghosh et al. Am J Hum Genet. 2000 Nov.

Abstract

We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Genomewide single-point association analysis and genomewide weighted and unweighted multipoint linkage analysis for type 2 diabetes, on chromosomes 1–8. In the linkage analysis, results are for the additive analysis. For association, the 2×N, best-allele, and high-versus-low analyses are shown for each marker.
Figure 2
Figure 2
Genomewide single-point association analysis and genomewide weighted and unweighted multipoint linkage analysis for type 2 diabetes, on chromosomes 9–22.
Figure 3
Figure 3
ASP linkage analysis and ordered-subsets–linkage results for type 2 diabetes. A, ASP linkage results for chromosome 6, for all families, for 94 families with the lowest fasting plasma-glucose levels, and for 74 families with the lowest age at onset. B, ASP linkage results for chromosome 10, for all families, for 40 families with the lowest IRI, for 75 families with the highest BMI, and for 28 families with the highest fasting C-peptide. C, ASP linkage results for chromosome 11.
Figure 4
Figure 4
Interaction-analysis plots for chromosome 20, conditional on chromosome 2. A, ASP linkage results for all families, for chromosome 2. B, ASP linkage results for chromosome 20. There is an increase in LOD score for chromosome 20, to 5.50 at 69.0 cM, when we condition on chromosome 2 at 8.5 cM.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Center for Medical Genetics, Marshfield Medical Research Foundation, http://research.marshfieldclinic.org/genetics
    1. Online Mendelian Inheritance in Man (OMIM), http://www3.ncbi.nlm.nih.gov/Omim/ (for uncoupling protein 2 [MIM 601693], pyruvate carboxylase [MIM 266150], and muscle glycogen phosphorylase [MIM 232600])
    1. Whitehead Institute for Biomedical Research/MIT Center for Genome Research, http://www-genome.wi.mit.edu/

References

    1. Bennett PH, Bogardus C, Tuomilehto J, Zimmett P (1992) Epidemiology and natural history of NIDDM: non-obese and obese. In: Alberti KGMM, DeFronzo RA, Keen H, Zimmett P (eds) International textbook of diabetes. John Wiley & Sons, New York, pp 147–176
    1. Boehnke M, Cox NJ (1997) Accurate inference of relationships in sib-pair linkage studies. Am J Hum Genet 61:423–429 - PMC - PubMed
    1. Boehnke M, The International Type 2 Diabetes Linkage Analysis Consortium (1998) Lessons learned in a combined linkage analysis (24 datasets, >2000 families) of type 2 diabetes on chromosome 20. Am J Hum Genet Suppl 63:A282
    1. Bowden DW, Sale M, Howard TD, Qadri A, Spray BJ, Rothschild CB, Akots G, Rich SS, Freedman BI (1997) Linkage of genetic markers on human chromosomes 20 and 12 to NIDDM in Caucasian sib pairs with a history of diabetic nephropathy. Diabetes 46:882–886 - PubMed
    1. Broman KW, Murray JC, Sheffield VC, White RL, Weber JL (1998) Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet 63:861–869 - PMC - PubMed

Publication types