The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. II. An autosomal genome scan for diabetes-related quantitative-trait loci

Richard M. Watanabe, Soumitra Ghosh, Carl D. Langefeld, Timo T. Valle, Elizabeth R. Hauser, Victoria L. Magnuson, Karen L. Mohlke, Kaisa Silander, Delphine S. Ally, Peter Chines, Jillian Blaschak-Harvan, Julie A. Douglas, William L. Duren, Michael P. Epstein, Tasha E. Fingerlin, Hong Shi Kaleta, Ethan M. Lange, Chun Li, Richard C. McEachin, Heather M. StringhamEdward Trager, Peggy P. White, James Balow, Gunther Birznieks, Jennie Chang, William Eldridge, Michael R. Erdos, Zarir E. Karanjawala, Julie I. Knapp, Kristina Kudelko, Colin Martin, Anabelle Morales-Mena, Anjene Musick, Tiffany Musick, Carrie Pfahl, Rachel Porter, Joseph B. Rayman, David Rha, Leonid Segal, Shane Shapiro, Ravi Sharaf, Ben Shurtleff, Alistair So, Joyce Tannenbaum, Catherine Te, Jason Tovar, Arun Unni, Christian Welch, Ray Whiten, Alyson Witt, Edna H. Ross, Elza Demirchyan, William A. Hagopian, Thomas A. Buchanan, Jaakko Tuomilehto, Richard N. Bergman, Francis S. Collins, Michael Boehnke

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Abstract

Type 2 diabetes mellitus is a complex disorder encompassing multiple metabolic defects. We report results from an autosomal genome scan for type 2 diabetes-related quantitative traits in 580 Finnish families ascertained for an affected sibling pair and analyzed by the variance components-based quantitative-trait locus (QTL) linkage approach. We analyzed diabetic and nondiabetic subjects separately, because of the possible impact of disease on the traits of interest. In diabetic individuals, our strongest results were observed on chromosomes 3 (fasting C-peptide/glucose: maximum LOD score [MLS] = 3.13 at 53.0 cM) and 13 (body-mass index: MLS = 3.28 at 5.0 cM). In nondiabetic individuals, the strongest results were observed on chromosomes 10 (acute insulin response: MLS = 3.11 at 21.0 cM), 13 (2-h insulin: MLS = 2.86 at 65.5 cM), and 17 (fasting insulin/glucose ratio: MLS = 3.20 at 9.0 cM). In several cases, there was evidence for overlapping signals between diabetic and nondiabetic individuals; therefore we performed joint analyses. In these joint analyses, we observed strong signals for chromosomes 3 (body-mass index: MLS = 3.43 at 59.5 cM), 17 (empirical insulin-resistance index: MLS = 3.61 at 0.0 cM), and 19 (empirical insulin-resistance index: MLS = 2.80 at 74.5 cM). Integrating genome-scan results from the companion article by Ghosh et al., we identify several regions that may harbor susceptibility genes for type 2 diabetes in the Finnish population.

Original languageEnglish (US)
Pages (from-to)1186-1200
Number of pages15
JournalAmerican journal of human genetics
Volume67
Issue number5
DOIs
StatePublished - Jan 1 2000

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Watanabe, R. M., Ghosh, S., Langefeld, C. D., Valle, T. T., Hauser, E. R., Magnuson, V. L., Mohlke, K. L., Silander, K., Ally, D. S., Chines, P., Blaschak-Harvan, J., Douglas, J. A., Duren, W. L., Epstein, M. P., Fingerlin, T. E., Kaleta, H. S., Lange, E. M., Li, C., McEachin, R. C., ... Boehnke, M. (2000). The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. II. An autosomal genome scan for diabetes-related quantitative-trait loci. American journal of human genetics, 67(5), 1186-1200. https://doi.org/10.1016/S0002-9297(07)62949-8