Familiality of Minimal Model-Derived Quantitative Metabolic Traits in a Finnish Cohort. Watanabe, R.M., Hauser, E.R., Valle, T., Eriksson, J., Bergman, R.N., Ghosh, S., and Boehnke, M. for the Finland-United States Investigation of NIDDM Genetics (FUSION) Study Investigators. Non-insulin dependent diabetes mellitus (NIDDM) is a complex disorder encompassing multiple metabolic defects. There exists strong evidence for a genetic component to NIDDM from twin and family studies; however, to date there have been few reports of linkage between genetic markers along the genome and NIDDM per se or with NIDDM-related quantitative traits (QTs). As part of the FUSION study, we sought to determine whether individual QTs, which determine glucose tolerance, exhibit familiality in this Finnish cohort. Tolbutamide-modified frequently-sampled intravenous glucose tolerance tests (FSIGT) were performed on unaffected offspring (n=431) and spouses (n=154) of affected sibling pairs sampled for the FUSION study. Minimal Model analyses were performed on FSIGT data to obtain quantitative measures of insulin sensitivity (SI), glucose effectiveness (SG), and insulin secretion assessed as the acute insulin response to glucose (AIR). The disposition index (DI), a measure of insulin resistance-corrected beta-cell function, was also derived as the product of SI and AIR. Variance components analysis was carried out using the computer program FISHER. Heritability (h2) for a given QT was estimated as the proportion of the total variance accounted for by the additive genetic variance component. The likelihood ratio statistic was used to compare models with and without the additive genetic variance component. After adjustment for age, gender, and body mass index, estimates for h2 were; SG: 18 plus or minus 9%, SI: 28 plus or minus 8%, AIR: 35 plus or minus 8%, DI: 23 plus or minus 8%. The fact that AIR showed the highest h2 is noteworthy since it has been hypothesized that beta-cell dysfunction is primarily responsible for NIDDM in the Finnish population. We conclude there is strong evidence for modest heritability of Minimal-Model derived NIDDM-related quantitative traits in the spouses and offspring of our Finnish affected sibling pairs.