Plasma HDL cholesterol, triglycerides, and adiposity. A quantitative genetic test of the conjoint trait hypothesis in the San Antonio Family Heart Study

Abstract

Background: The conjoint trait hypothesis proposes that combined low HDL cholesterol (HDL-C) and high triglyceride (TG) levels represent a single, inherited phenotype that adiposity may influence in an unspecified manner. We conducted formal statistical genetic tests of the conjoint trait hypothesis and the relation of the conjoint trait to adiposity using data for 569 subjects in 25 pedigrees from the San Antonio Family Heart Study.

Methods and results: We conducted multivariate genetic analyses to detect the effects of genes and environmental factors on variation in plasma concentrations of HDL-C and TG, fat mass (as percent body weight [FM%], determined by bioelectric impedance), and body mass index (BMI). We used maximum-likelihood methods to simultaneously estimate the phenotypic means and SDs, heritabilities (h2), effects of sex, age-by-sex, eight dietary and medical covariates, and genetic and environmental correlations. Likelihood ratio tests disclosed significant heritabilities (P < .001) for all traits (h2HDL-C = 0.55, h2TG = 0.53, h2FM% = 0.37, h2BMI = 0.44) but significant genetic correlations (P < .001), indicating pleiotropy, between two trait pairs only: HDL-C and TG (PG = -0.52) and fat mass and BMI (PG = 0.86). We obtained significant environmental correlations between all trait pairs except HDL-C and BMI (P > .05).

Conclusions: Both shared genes (pleiotropy) and shared environmental factors contribute to the commonly observed inverse phenotypic association between plasma levels of HDL-C and TG. Rather than low HDL-C and high TG being a single, genetically transmissible entity, it is the inverse relation between these two phenotypes throughout their normal ranges of variation as well as at the extremes that is influenced by shared genes and shared environments. However, common environmental factors, not shared genes, account for reported associations of plasma HDL-C and TG levels with measures of adiposity.