Genome scan results of an independent set of Finnish affected sibling pairs with type 2 diabetes. K. Silander1, R. Watanabe2, T. Valle3, K. Mohlke1, H. Stringham2, K. Doheny4, E. Pugh4, R. Bergman5, J. Tuomilehto3, F. Collins1, M. Boehnke2, and The FUSION Study Group1,2,3,5. 1) NHGRI, NIH, Bethesda, MD; 2) Department of Biostatistics, University of Michigan, Ann Arbor, MI; 3) Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland; 4) Center for Inherited Disease Research, Johns Hopkins University School of Medicine, Baltimore, MD; 5) Keck School of Medicine, University of Southern California, Los Angeles, CA.

   The Finland-U.S. Investigation of NIDDM Genetics (FUSION) study is an international collaboration that aims to map and positionally clone type 2 diabetes susceptibility genes. In an initial genome-wide scan we studied 719 affected sibling pairs from 478 Finnish families. This first set of families showed strongest evidence for linkage on chromosome 20, with weighted maximum lod scores (MLSs) of 1.99 at 17.5 cM, 2.04 at 56.5 cM, and 2.15 at 69.5 cM. An additional interesting locus was on chromosome 11 at 84 cM (MLS=1.75). We now have collected a second, independent set of 240 Finnish affected sib pair families (a total of 441 affected sib pairs). The two sets of patients were ascertained in a similar manner. However, the second set of patients has slightly shorter mean duration of disease (11.4 vs. 12.3 years) and lower mean fasting glucose values (9.3 vs. 10.4 mM). We have now completed genotyping of 382 markers for a genome scan on this second sample, in addition to typing 43 chromosome 20 markers, and have begun to analyze the resulting data. Our preliminary findings for the second sample provide additional evidence for a locus on 20p (MLS = 0.56 at 20.5 cM), but not for the other two chromosome 20 linkage peaks. When the two data sets are combined with additional affected siblings, removing the 10% of individuals with the self-reported earliest age of diagnosis increases the MLS to 3.58 at 17 cM. Statistical analysis of the remainder of the genome scan data is ongoing.