Abstract 19528: Parent of Origin Effect in Lipid Profiles
Even though heritability estimates for lipid traits are high (40-60% for HDL and 40-50% for LDL), genetic contributions to lipid expression are complex and are not fully understood. Part of this variability may be due to epigenetic influences such as genomic imprinting; maternal hypercholesterolemia is thought to influence in offspring cardiovascular outcomes even in adult life. Such epigenetic factors can be observed as parent of origin effects within families. To explore this mechanism in lipid traits, we examined natural lipid variation that can be explained by parent of origin effects in the general population. We performed linear regressions in the second and third generations from the Framingham Cohort (n= 9,219 participants) to compare lipid trait correlations between mothers and daughter, mothers and sons, fathers and daughters, and fathers and sons with the goal of identifying sex-specific transmission effects. Models were adjusted for BMI, age, smoking status, treatment, and menopausal status of both parent and offspring. We performed a likelihood ratio test to compare a reduced model (containing offspring and parent covariates only) to a full model that includes parent lipid values as a risk factor. As anticipated, we observe that a significant amount of offspring HDL and LDL is explained by parent HDL/LDL levels. However, we also note that maternal HDL and LDL levels explain significantly more variance in daughter HDL and LDL compared to other models of other parent/offspring pairs, with the full model showing R2=0.19 versus a reduced model with R2=0.12 (chi2 = 104.9 and p=1.285e-24) for HDL a full model showing R2=0.17 versus a reduced model with R2=0.11 (chi2 = 84.0 and p=4.948e-20) for LDL. By contrast, the relationship between maternal HDL explains only 2% of the son’s HDL (LR=19.74, p<8.872e-6) and the relationship between maternal LDL explains only 3% of the son’s LDL.
- © 2012 by American Heart Association, Inc.