Pleiotropic genetic effects on LDL size, plasma, triglyceride, and HDL cholesterol in families

The interrelationships among low density lipoprotein (LDL) particle size, p lasma triglyceride (TG), and high density lipoprotein cholesterol (HDL-C) a re:well established and may involve underlying genetic influences. This stu dy evaluated common genetic effects on LDL size, TG, and HDL-C by using dat a from 85 kindreds participating in the Genetic Epidemiology of Hypertrigly ceridemia (GET) Study. A multivariate, maximum likelihood-based approach to quantitative genetic analysis was used to estimate the additive effects of shared genes and shared, unmeasured nongenetic factors on variation in LDL size and in plasma levels of TG and HDL-C. A significant (P<0.001) proport ion of the variance in each trait was attributable to the additive effects of genes. Maximum-likelihood estimates of heritability were 0.34 for LDL si ze 0.41 for TG, and 0.54 for HDL-C. Significant (P<0.001) additive genetic correlations (rho(G)), indicative-of the shared additive effects of genes o n pairs of traits, were estimated between all 3 trait pairs: for LDL size a nd TC rho(G)=-0.87, for LDL. size and HDL-C rho(G)=0.65, and for HDL-C and TC rho(G)=-0.54. A similar pattern of significant environmental correlation s between the 3 trait pairs was also observed. These results suggest that a large proportion of the well-documented correlations in LDL size, TC, and HDL-C are likely attributable to the influence of the same gene(s) in these families. That is,the gene(s) that may contribute to decreases in LDL size also contribute significantly to higher plasma levels of TG and lower plas ma levels of HDL-C. These relationships may be useful in identifying genes responsible for the associations between these phenotypes and susceptibilit y to cardiovascular disease in these families.