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