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

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 positi on 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 m odel. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 2 0 increases to 5.50 at 69.0 cM (P = .0014). An ordered-subsets analysis bas ed on families with high or low diabetes-related quantitative traits yielde d 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 D22S 423 (P = .00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes.