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P13 The Insulin Resistance Syndrome (IRS) increases risk for both  cardiovascular disease (CVD) and diabetes. While the underlying defect  may be insulin resistance itself, others have suggested that central  adiposity is the primary defect. Further, these risk factors are highly  interrelated, but it is not known if genetic and/or environmental  factors influence this relationship. The purpose of this analysis was  to evaluate evidence for shared genetic and environmental effects on  the covariation of fasting plasma insulin level (FI), a marker for  insulin resistance, and waist circumference (WC) in 315 Japanese  Americans with complete data (in 38 families) participating in the  Japanese American Family Study, in Seattle. Subjects ranged in age from  18-94 (mean=54.8, SD=16), and 52% were female. Insulin was measured  from a fasting blood sample, and waist circumference was self-measured  using a tape measure and specific instructions provided to each  participant. Quantitative genetic analysis was used to evaluate genetic  (ρ G ) and environmental (ρ E ) correlations  between FI and WC, adjusting for age, gender, and body mass index. A  significant (p&lt;0.05) proportion of the variance in each trait was  attributable to additive genetic effects: heritability =0.29 and 0.23  for FI and WC, respectively. The strong and significant (p&lt;0.01)  ρ G =0.83 reflects shared genetic influences between FI and  WC, indicating that the majority of genes that influence FI also  influence WC. Further, ρ G was not significantly different  from 1.0, suggesting the possibility of nearly complete genetic  pleiotropy between these risk factors (i.e. that FI and WC share all  their genes in common). Estimated ρ E =-0.08, but was not significantly different from zero. These results are the  first to suggest complete pleiotropy between FI and WC. Incorporating  these results into future gene mapping studies should increase power to  detect susceptibility genes for not only CVD and diabetes, but also  central adiposity.

Common Genetic Influences on fasting insulin and waist circumference: The Japanese American Family Study