TY - JOUR
T1 - 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
AU - Watanabe, Richard M.
AU - Ghosh, Soumitra
AU - Langefeld, Carl D.
AU - Valle, Timo T.
AU - Hauser, Elizabeth R.
AU - Magnuson, Victoria L.
AU - Mohlke, Karen L.
AU - Silander, Kaisa
AU - Ally, Delphine S.
AU - Chines, Peter
AU - Blaschak-Harvan, Jillian
AU - Douglas, Julie A.
AU - Duren, William L.
AU - Epstein, Michael P.
AU - Fingerlin, Tasha E.
AU - Kaleta, Hong Shi
AU - Lange, Ethan M.
AU - Li, Chun
AU - McEachin, Richard C.
AU - Stringham, Heather M.
AU - Trager, Edward
AU - White, Peggy P.
AU - Balow, James
AU - Birznieks, Gunther
AU - Chang, Jennie
AU - Eldridge, William
AU - Erdos, Michael R.
AU - Karanjawala, Zarir E.
AU - Knapp, Julie I.
AU - Kudelko, Kristina
AU - Martin, Colin
AU - Morales-Mena, Anabelle
AU - Musick, Anjene
AU - Musick, Tiffany
AU - Pfahl, Carrie
AU - Porter, Rachel
AU - Rayman, Joseph B.
AU - Rha, David
AU - Segal, Leonid
AU - Shapiro, Shane
AU - Sharaf, Ravi
AU - Shurtleff, Ben
AU - So, Alistair
AU - Tannenbaum, Joyce
AU - Te, Catherine
AU - Tovar, Jason
AU - Unni, Arun
AU - Welch, Christian
AU - Whiten, Ray
AU - Witt, Alyson
AU - Ross, Edna H.
AU - Demirchyan, Elza
AU - Hagopian, William A.
AU - Buchanan, Thomas A.
AU - Tuomilehto, Jaakko
AU - Bergman, Richard N.
AU - Collins, Francis S.
AU - Boehnke, Michael
N1 - Funding Information:
The authors thank the thousands of Finnish citizens who volunteered to participate in the FUSION study. We also gratefully acknowledge the hard work of the numerous field workers in Finland, as well as the work of Paula Nyholm, Jouko Sundvall, Tuula Tenkula, and Sanelma Vilkkilä. We would also like to thank Darryl Leja at the National Human Genome Research Institute (NHGRI) for his assistance in preparing the figures for this article. This project was made possible by intramural funds from NHGRI project OH95-C-N030 and by NIH grant HG00376 (to M.B.); the project was also partly supported by the Finnish Academy. Family studies were approved by institutional review boards at the NIH (assurance number SPA S-5737-05) and at the National Public Health Institute in Helsinki. R.M.W. was previously supported by individual NIH National Research Service Award DK09525 and is now supported by a Career Development Award from the American Diabetes Association. R.N.B. is supported by NIH grants DK27619 and DK29867. C.D.L., J.A.D., W.L.D., M.P.E., E.M.L., and H.M.S. were previously supported, and T.E.F. and R.C.M. are currently supported, by NIH training grant HG00040.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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U2 - 10.1016/S0002-9297(07)62949-8
DO - 10.1016/S0002-9297(07)62949-8
M3 - Article
C2 - 11032784
AN - SCOPUS:0033758721
SN - 0002-9297
VL - 67
SP - 1186
EP - 1200
JO - American journal of human genetics
JF - American journal of human genetics
IS - 5
ER -