Genetic control of coordinated changes in HDL and LDL size phenotypes

We investigated the correlation of high density lipoprotein (HDL) and low d ensity lipoprotein (LDL) particle size distributions in samples from > 1100 participants in the San Antonio Family Heart Study. By use of analyses of individual correlations of each HDL fraction with each LDL fraction, we dev ised new metrics for particle size phenotype, termed Delta HDL and Delta LD L, to optimally reflect the size correlations. Confirming previous studies, we found that the 2 size phenotype variables were positively correlated (r = 0.51). Quantitative genetic analysis indicated that nearly half (44%) of the variance in Delta HDL and in Delta LDL was explained by the additive e ffects of genes. Bivariate genetic analyses indicated that a positive genet ic correlation (rho (G) = 0.56) exists between them and suggested that the pleiotropic effects of a gene or group of genes account for approximate to 31% [ie, rho (2)(G) = (0.56)(2) = 0.31] of the genetic variance in the 2 tr aits. Triglyceride (TG) levels were negatively related to Delta HDL and Del ta LDL, with phenotypic correlations of -0.48 and -0.58, respectively, and genetic correlations of -0.45 and -0.76, respectively, suggesting that gene s exert significant pleiotropic effects on the covariation of TGs with each of the size variables. Finally, we evaluated a bivariate model for Delta H DL and Delta LDL in which TG level was included as a covariate. This analys is indicated that a small but significant genetic correlation remains for D elta HDL and Delta LDL, even after accounting for the effects of TGs. Thus, our study demonstrates that the phenotypic correlation of HDL and LDL size s results in part from the pleiotropic actions of a set of genes, some of w hich also influence TG levels and some of which do not.