(Circulation. 1995;92:3240-3248.)
© 1995 American Heart Association, Inc.
Articles |
Plasma HDL Cholesterol, Triglycerides, and Adiposity
A Quantitative Genetic Test of the Conjoint Trait Hypothesis in the San Antonio Family Heart Study
From the Department of Genetics, Southwest Foundation for Biomedical Research (M.C.M., J.B., A.G.C., J.L.B, J.W.M.) and Division of Epidemiology, University of Texas Health Science Center at San Antonio (M.P.S.).
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 (
G=-0.52) and
fat mass and BMI (G=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.
Key Words: genetics • lipids • lipoproteins • obesity
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