Abstract 12991: Dissecting the Parent-of-origin Effect on Lipid Traits: From Genes to Environment
The roles played by genetic and environmental factors in the regulation of plasma lipid levels are complex and intertwined. Heritability estimates range from 40 to 60% for HDL, 40 to 50% for LDL, and 35 to 48% for triglycerides. Nevertheless, no more than 12% of the total phenotypic variance in HDL and LDL is explained by all of the gene variants known to be associated with lipids in the Framingham cohort.
Using data from the last two generations from the Framingham cohort, we previously demonstrated that the addition of non-genetic factors to parental lipid levels significantly improves the prediction of lipid levels in the offspring, allowing us to explain up to 39% of the phenotypic variance in the same dataset. The lipoprotein levels of both parents are significantly predictive of the offspring’s levels. With this a priori knowledge, the current study aimed at identifying the cause of the parent-of-origin effect.
To assess the role of shared environment as compared to shared genetics, we first analyzed lipoprotein correlations between parents from Generation 2 (n=992) and compared such correlations to those observed previously between parental and offspring groups. We assume that a set of parents shares the same environment, but not the same genetics. Correlations (R2) were adjusted for BMI, age, smoking status, and menopausal status.
To investigate the source of the parental effect, we then conducted a transmission disequilibrium test between mothers and daughters (n=480) and fathers and sons (n=410) for each one of the traits.
The lipid and lipoprotein correlations between mother and father in each couple were significant, but up to 10-fold lower than that obtained between parents and offspring.
Several polymorphisms appeared to contribute to the parent-of-origin effect on lipoproteins (threshold p ≤ e-6). In addition to some genes that had been previously associated to lipid traits or BMI, many novel genes were found with potential functional roles.
Although significant, environment is a relatively minor contributor to the parent-of-origin effect on plasma lipid and lipoprotein levels, thus leaving the leading role to other mechanisms, likely based on interactions of genetic and epigenetic agents.
- © 2013 by American Heart Association, Inc.