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

Soumitra Ghosh, Richard M. Watanabe, Timo T. Valle, Elizabeth R. Hauser, Victoria L. Magnuson, Carl D. Langefeld, Delphine S. Ally, Karen L. Mohlke, Kaisa Silander, Kimmo Kohtamaki, Peter Chines, James Balow, Gunther Birznieks, Jennie Chang, William Eldridge, Michael R. Erdos, Zarir E. Karanjawala, Julie I. Knapp, Kristina Kudelko, Colin MartinAnabelle 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, 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. Stringham, Edward Trager, Peggy P. White, Johan Eriksson, Liisa Toivanen, Gabriele Vidgren, Stella J. Nylund, Eva Tuomilehto-Wolf, Edna H. Ross, Elza Demirchyan, William A. Hagopian, Thomas A. Buchanan, Richard N. Bergman, Francis S. Collins, Michael Boehnke

Research output: Contribution to journalArticle

209 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1174-1185
Number of pages12
JournalAmerican Journal of Human Genetics
Volume67
Issue number5
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

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Chromosomes, Human, Pair 20
Chromosomes, Human, Pair 2
Finland
Type 2 Diabetes Mellitus
Genome
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 6
Linkage Disequilibrium
Microsatellite Repeats
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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. / Ghosh, Soumitra; Watanabe, Richard M.; Valle, Timo T.; Hauser, Elizabeth R.; Magnuson, Victoria L.; Langefeld, Carl D.; Ally, Delphine S.; Mohlke, Karen L.; Silander, Kaisa; Kohtamaki, Kimmo; Chines, Peter; 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; Harvan, Jillian Blaschak; 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.; Eriksson, Johan; Toivanen, Liisa; Vidgren, Gabriele; Nylund, Stella J.; Tuomilehto-Wolf, Eva; Ross, Edna H.; Demirchyan, Elza; Hagopian, William A.; Buchanan, Thomas A.; Bergman, Richard N.; Collins, Francis S.; Boehnke, Michael.

In: American Journal of Human Genetics, Vol. 67, No. 5, 01.01.2000, p. 1174-1185.

Research output: Contribution to journalArticle

Ghosh, S, Watanabe, RM, Valle, TT, Hauser, ER, Magnuson, VL, Langefeld, CD, Ally, DS, Mohlke, KL, Silander, K, Kohtamaki, K, Chines, P, 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, Harvan, JB, Douglas, JA, Duren, WL, Epstein, MP, Fingerlin, TE, Kaleta, HS, Lange, EM, Li, C, McEachin, RC, Stringham, HM, Trager, E, White, PP, Eriksson, J, Toivanen, L, Vidgren, G, Nylund, SJ, Tuomilehto-Wolf, E, Ross, EH, Demirchyan, E, Hagopian, WA, Buchanan, TA, Bergman, RN, Collins, FS & Boehnke, M 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', American Journal of Human Genetics, vol. 67, no. 5, pp. 1174-1185. https://doi.org/10.1016/S0002-9297(07)62948-6
Ghosh, Soumitra ; Watanabe, Richard M. ; Valle, Timo T. ; Hauser, Elizabeth R. ; Magnuson, Victoria L. ; Langefeld, Carl D. ; Ally, Delphine S. ; Mohlke, Karen L. ; Silander, Kaisa ; Kohtamaki, Kimmo ; Chines, Peter ; 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 ; Harvan, Jillian Blaschak ; 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. ; Eriksson, Johan ; Toivanen, Liisa ; Vidgren, Gabriele ; Nylund, Stella J. ; Tuomilehto-Wolf, Eva ; Ross, Edna H. ; Demirchyan, Elza ; Hagopian, William A. ; Buchanan, Thomas A. ; Bergman, Richard N. ; Collins, Francis S. ; Boehnke, Michael. / 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. In: American Journal of Human Genetics. 2000 ; Vol. 67, No. 5. pp. 1174-1185.
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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.",
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T1 - 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

AU - Ghosh, Soumitra

AU - Watanabe, Richard M.

AU - Valle, Timo T.

AU - Hauser, Elizabeth R.

AU - Magnuson, Victoria L.

AU - Langefeld, Carl D.

AU - Ally, Delphine S.

AU - Mohlke, Karen L.

AU - Silander, Kaisa

AU - Kohtamaki, Kimmo

AU - Chines, Peter

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 - Harvan, Jillian Blaschak

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 - Eriksson, Johan

AU - Toivanen, Liisa

AU - Vidgren, Gabriele

AU - Nylund, Stella J.

AU - Tuomilehto-Wolf, Eva

AU - Ross, Edna H.

AU - Demirchyan, Elza

AU - Hagopian, William A.

AU - Buchanan, Thomas A.

AU - Bergman, Richard N.

AU - Collins, Francis S.

AU - Boehnke, Michael

PY - 2000/1/1

Y1 - 2000/1/1

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AB - 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.

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