THE FUSION (FINLAND-UNITED STATES INVESTIGATION OF NIDDM GENETICS) STUDY. 
S. Ghosh 1, E. Hauser 2, V. Magnuson 1, T. Valle 3, D. Ally 1, R. Watanabe 2,
W. Hagopian 4, R. Bergman 5, J. Tuomilehto 3, F. Collins 1, and M. Boehnke 2
for the FUSION team. 1 NHGRI, NIH, Bethesda, Maryland; 2 University of
Michigan, Ann Arbor, Michigan; 3 National Public Health Institute, Helsinki,
Finland; 4 University of Washington, Seattle, Washington; 5 University of
Southern California School of Medicine, Los Angeles, California.

The FUSION study is a collaborative effort to map genes for NIDDM (non-insulin
dependent diabetes mellitus) in the Finnish population.  We are performing a
genome scan using approximately 400 microsatellite markers in 710 NIDDM-
affected sib pairs (ASPs) from 473 families to create a map with an average
average resolution of 10cM. Using criteria based on serum C-peptide levels, GAD
autoantibodies and the use of insulin medication in diabetics, we have
excluded 43 families with possible late-onset IDDM. In 183 families we are also
typing the spouse and offspring (n=446) of one of the affected sibs while
measuring insulin sensitivity and plasma insulin response in these unaffected
family members using a frequently sampled intravenous glucose tolerance test
and the minimal model. 220 unaffected controls mean age 70 years are also
being studied. More than 800,000 first-pass genotypings have been completed
so far with an average error rate of 0.12% based on duplicate samplies.  Our
present sustainable rate is 25,000 genotypes per week.  Our analysis strategy
includes non-parametric, multi-point identity-by-descent and single-point
identity-by-state methods and association analyses. We can exclude linkage on
chromosomes 1, 5, 6, 7, 8, 12, 13, 15, 16, 19, 21 and 22 for diabetes at a
lambda(s) value of 1.55, while chromosome 2 can be excluded at 1.9 and
chromosome 20 at 2.1, all under an additive model.  At present, data for
chromosomes 9, 10, and 11 are being analyzed while most of chromosomes 3, 4,
and 14 have also been typed. The genome scan should be complete by fall
of 1997.