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 A 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

Research output: Contribution to journalArticle

124 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Quantitative Trait Loci
Finland
Type 2 Diabetes Mellitus
Chromosomes, Human, Pair 3
Genome
Insulin
Insulin Resistance
Fasting
Body Mass Index
Joints
Glucose
Chromosomes, Human, Pair 10
C-Peptide
Population
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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

In: American Journal of Human Genetics, Vol. 67, No. 5, 01.01.2000, p. 1186-1200.

Research output: Contribution to journalArticle

Watanabe, RM, Ghosh, S, Langefeld, CD, Valle, TT, Hauser, ER, Magnuson, VL, Mohlke, KL, Silander, K, Ally, DS, Chines, P, Blaschak-Harvan, J, Douglas, JA, Duren, WL, Epstein, MP, Fingerlin, TE, Kaleta, HS, Lange, EM, Li, C, McEachin, RC, Stringham, HM, Trager, E, White, PP, Balow, J, Birznieks, G, Chang, J, Eldridge, W, Erdos, MR, Karanjawala, ZE, Knapp, JI, Kudelko, K, Martin, C, Morales-Mena, A, Musick, A, Musick, T, Pfahl, C, Porter, R, Rayman, JB, Rha, D, Segal, L, Shapiro, SA, Sharaf, R, Shurtleff, B, So, A, Tannenbaum, J, Te, C, Tovar, J, Unni, A, Welch, C, Whiten, R, Witt, A, Ross, EH, Demirchyan, E, Hagopian, WA, Buchanan, TA, Tuomilehto, J, Bergman, RN, Collins, FS & 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, vol. 67, no. 5, pp. 1186-1200. https://doi.org/10.1016/S0002-9297(07)62949-8
Watanabe, Richard M. ; Ghosh, Soumitra ; Langefeld, Carl D. ; Valle, Timo T. ; Hauser, Elizabeth R. ; Magnuson, Victoria L. ; Mohlke, Karen L. ; Silander, Kaisa ; Ally, Delphine S. ; Chines, Peter ; Blaschak-Harvan, Jillian ; Douglas, Julie A. ; Duren, William L. ; Epstein, Michael P. ; Fingerlin, Tasha E. ; Kaleta, Hong Shi ; Lange, Ethan M. ; Li, Chun ; McEachin, Richard C. ; Stringham, Heather M. ; Trager, Edward ; White, Peggy P. ; Balow, James ; Birznieks, Gunther ; Chang, Jennie ; Eldridge, William ; Erdos, Michael R. ; Karanjawala, Zarir E. ; Knapp, Julie I. ; Kudelko, Kristina ; Martin, Colin ; Morales-Mena, Anabelle ; Musick, Anjene ; Musick, Tiffany ; Pfahl, Carrie ; Porter, Rachel ; Rayman, Joseph B. ; Rha, David ; Segal, Leonid ; Shapiro, Shane A ; Sharaf, Ravi ; Shurtleff, Ben ; So, Alistair ; Tannenbaum, Joyce ; Te, Catherine ; Tovar, Jason ; Unni, Arun ; Welch, Christian ; Whiten, Ray ; Witt, Alyson ; Ross, Edna H. ; Demirchyan, Elza ; Hagopian, William A. ; Buchanan, Thomas A. ; Tuomilehto, Jaakko ; Bergman, Richard N. ; Collins, Francis S. ; Boehnke, Michael. / 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. In: American Journal of Human Genetics. 2000 ; Vol. 67, No. 5. pp. 1186-1200.
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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.",
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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 A

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

PY - 2000/1/1

Y1 - 2000/1/1

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.

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