TY - JOUR
T1 - Genetic control of coordinated changes in HDL and LDL size phenotypes
AU - Rainwater, David L.
AU - Martin, Lisa J.
AU - Comuzzie, Anthony G.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - We investigated the correlation of high density lipoprotein (HDL) and low density 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 devised new metrics for particle size phenotype, termed ΔHDL and ΔLDL, 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 ΔHDL and in ΔLDL was explained by the additive effects of genes. Bivariate genetic analyses indicated that a positive genetic correlation (ρG=0.56) exists between them and suggested that the pleiotropic effects of a gene or group of genes account for ≅31% [ie, ρG2 = (0.56)2=0.31 ] of the genetic variance in the 2 traits. Triglyceride (TG) levels were negatively related to ΔHDL and ΔLDL, with phenotypic correlations of -0.48 and -0.58, respectively, and genetic correlations of -0.45 and -0.76, respectively, suggesting that genes exert significant pleiotropic effects on the covariation of TGs with each of the size variables. Finally, we evaluated a bivariate model for ΔHDL and ΔLDL in which TG level was included as a covariate. This analysis indicated that a small but significant genetic correlation remains for ΔHDL and ΔLDL, even after accounting for the effects of TGs. Thus, our study demonstrates that the phenotypic correlation of HDL and LDL sizes results in part from the pleiotropic actions of a set of genes, some of which also influence TG levels and some of which do not.
AB - We investigated the correlation of high density lipoprotein (HDL) and low density 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 devised new metrics for particle size phenotype, termed ΔHDL and ΔLDL, 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 ΔHDL and in ΔLDL was explained by the additive effects of genes. Bivariate genetic analyses indicated that a positive genetic correlation (ρG=0.56) exists between them and suggested that the pleiotropic effects of a gene or group of genes account for ≅31% [ie, ρG2 = (0.56)2=0.31 ] of the genetic variance in the 2 traits. Triglyceride (TG) levels were negatively related to ΔHDL and ΔLDL, with phenotypic correlations of -0.48 and -0.58, respectively, and genetic correlations of -0.45 and -0.76, respectively, suggesting that genes exert significant pleiotropic effects on the covariation of TGs with each of the size variables. Finally, we evaluated a bivariate model for ΔHDL and ΔLDL in which TG level was included as a covariate. This analysis indicated that a small but significant genetic correlation remains for ΔHDL and ΔLDL, even after accounting for the effects of TGs. Thus, our study demonstrates that the phenotypic correlation of HDL and LDL sizes results in part from the pleiotropic actions of a set of genes, some of which also influence TG levels and some of which do not.
KW - Genetics
KW - HDL size distributions
KW - LDL size distributions
KW - Mexican Americans
KW - Triglycerides
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U2 - 10.1161/hq1101.0908551
DO - 10.1161/hq1101.0908551
M3 - Article
C2 - 11701473
AN - SCOPUS:0035571585
VL - 21
SP - 1829
EP - 1833
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 11
ER -