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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 Ghosh, S., Watanabe, R. M., Valle, T. T., Hauser, E. R., Magnuson, V. L., Langefeld, C. D., Ally, D. S., Mohlke, K. L., Silander, K., Kohtamaki, K., Chines, P., Balow, J., Birznieks, G., Chang, J., Eldridge, W., Erdos, M. R., Karanjawala, Z. E., Knapp, J. I., Kudelko, K., Martin, C., Morales-Mena, A., Musick, A., Musick, T., Pfahl, C., Porter, R., Rayman, J. B., Rha, D., Segal, L., Shapiro, S., Sharaf, R., Shurtleff, B., So, A., Tannenbaum, J., Te, C., Tovar, J., Unni, A., Welch, C., Whiten, R., Witt, A., 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., Stringham, H. M., Trager, E., White, P. P., Eriksson, J., Toivanen, L., Vidgren, G., NYLUND, S. J., Tuomilehto-Wolf, E., Ross, E. H., Demirchyan, E., Hagopian, W. A., Buchanan, T. A., Tuomilehto, J., Bergman, R. N., Collins, F. S., Boehnke, M. 2000; 67 (5): 1174-1185

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.

View details for Web of Science ID 000165091600015

View details for PubMedID 11032783