Genetic correlations between lipoprotein phenotypes and indicators of sex hormone levels in Mexican Americans

Previous studies have shown that the inverse relationship between HDL cholesterol (HDL-C) and triglyceride (TG) levels, risk factors for cardiovascular disease, is due largely to the effects of shared genes. HDL-C and TG are also known to be related to endogenous sex hormone levels, however,the nature of the relationships is unclear. The objective of this study is to ascertain the extent to which these relationships are determined by shared genes. We conducted a multivariate quantitative genetic analysis of HDL-C, TG, dehydroepiandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) in 635 people from 27 pedigrees participating in the San Antonio Family Heart Study. Heritabilities (h²) and genetic and environmental correlations (ρ(G) and ρ(E)) were estimated simultaneously by maximum likelihood methods. All four traits showed significant (P < 0.05) heritabilities: h²(HDL-C) = 0.38, h²(TG) = 0.54, h²(DHEAS) = 0.43 and h²(SHBG) = 0.26. Significant genetic correlations were detected between HDL and each of the other traits: ρ(G(HDL-TG)) = -0.56, ρ(G(HDL-DHEAS)) = 0.23 and ρ(G(HDL-SHBG) = -0.56. However, there were no significant genetic correlations between TG and either measure of sex hormones. Thus, at least three separate groups of genes influence HDL-C levels in Mexican Americans: one group that has pleiotropic effects on HDL and TG, one group influences both HDL-C and SHBG and a third influences both HDL-C and DHEAS.