Tel-Aviv-Heidelberg Three Generation Offspring Study: Genetic and Environmental Sources of Variation and Covariation among Plasma Lipids, Lipoproteins, and Apoliproteins

Multivariate genetic analysis, implemented in the statistical package for pedigree analysis, FISHER, was carried out on a large sample of Israeli pedigrees to evaluate heritability and genetic correlations among an array of plasma lipids: total cholesterol (TCHL), triglycerides (TRIG), HDL-C and HDL2-C, HDL3-C, LDL-C and HDL-C%, apolipoproteins A and B (APO-A1 and APO-B), lipoprotein LP(a) and fibrinogen (FIBR). Multiple regression analysis showed that although sex, age, smoking and other study environmental factors, have a significant contribution to the variation of each plasma lipid they exert little effect on covariation in lipids. Genes, however, are important factors of the variation and covariation in lipids. Thus, variance component analysis showed that the genetic component of the study variables, adjusted on age, sex and environmental factors, ranged between 31% for logarithm-transformed TRIG and 77% for plasma concentrations of LP(a). Coefficients of multiple genetic determination of the genetic variation of each variable attributable to all of the other variables, ranged from low values (<30%) for TRIG, LP(a) and FIBR, to moderate (64%) for HDL2-C. The genetic variation of each of the remaining variables was completely explained by variation in other lipids. The results of a factor analyses of phenotypic, genetic and environmental correlation matrices were similar and clearly identified several clusters of variables. The first included APO-A1, HDL-C, HDL2-C and HDL3-C, and the second-APO-B, LDL-C and THCL. Further analysis showed that it was probable the genetic component of variation of HDL3-C plasma concentration that fully depended on APO-A1, while those of LDL-C and TCHL fully depended on APO-B. The degree of correlation between TRIG, LP(a), FIBR and other variables, if any, was considerably lower.