Familiality of Quantitative Metabolic Traits in a Finnish Population.
RICHARD M. WATANABE*, ELIZABETH R. HAUSER, TIMO VALLE, JOHAN ERIKSSON*, 
RICHARD N. BERGMAN*, AND MICHAEL BOEHNKE FOR THE FINLAND-UNITED STATES  
INVESTIGATION OF NIDDM GENES (FUSION) STUDY INVESTIGATORS.  Ann Arbor, 
MI; Helsinki, Finland; and Los Angeles, CA.

Non-insulin dependent diabetes mellitus (NIDDM) is a complex disorder 
encompassing multiple metabolic defects.  To date there has not been 
convincing evidence for linkage between genetic markers along the genome 
and NIDDM per se or NIDDM-related quantitative traits (QT).  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 in offspring (n=369) and spouses (n=141) of 
affected sibling pairs identified 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 b-cell 
function, was also derived as SIxAIR.  For each QT, one-way analysis of 
variance was performed on values obtained from offspring using families 
with more than one offspring, adjusting for age, gender, and body mass 
index.  Significant familial aggregation was observed for each trait in 
offspring of the 126 families tested (See Table).  However, significant 
correlations were also noted among the QTs examined.  When analyses were 
repeated further adjusting for the other 2 traits (e.g., SG adjusting 
for SI and AIR), evidence for familiality persisted.  We conclude there 
exists familiality for Minimal Model derived quantitative traits in the 
offspring of our Finnish affected sibling pairs.

Trait	F-value	p-value
SG	    1.40	0.016
SI	    1.32	0.038
AIR	    1.73	0.003
DI	    1.48	0.007