OR05-1 ENVIRONMENTAL EFFECTS ON PLASMA LIPIDS IN THE FRAMINGHAM COHORT

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR05-Lipids: Regulation & Mechanism of Disease
Basic/Clinical
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 11:30 AM
Room 133 (Moscone Center)
Jessica Sparks Lilley*1, Irene Marta Predazzi2, William Scott Bush2, Mac Rae F Linton3, Sergio Fazio4 and Scott M Williams5
1Vanderbilt Children's Pediat, Nashville, TN, 2Vanderbilt University School of Medicine, 3Vanderbilt Univ Sch of Med, Nashville, TN, 4Vanderbilt Univ, Nashville, TN, 5Dartmouth Medical School
Introduction:  The roles of genetic and environmental contributions to plasma lipid levels are complex and not fully understood. Heritability estimates are about 40-50% for HDL,1 but only 10-12% of the total variance has been accounted for by individual genes.2 Part of the missing variance can be attributed to epigenetic influences since the maternal environment has been shown to affect fetal outcomes in a variety of disease processes, from diabetes to cancer to psychiatric illness.  Maternal hypercholesterolemia is thought to affect children’s cardiovascular outcomes in adulthood, though animal and epidemiologic studies have produced conflicting results.  We recently have determined that parental lipid parameters strongly influence levels of LDL-C, HDL-C, and TG in the offspring, even when correcting for known confounders.3 These results, however, do not account for the impact of potential shared environment. The Framingham Heart Study (FHS) provides a means to examine a large cohort of parents and their offspring. Though parents and offspring no longer shared a household at the time of their inclusion in the study, parents most likely lived together at the time of their enrollment and can serve as internal controls for the effects of shared environment.   

Objective:To determine the impact of the environment on lipid parameters of couples in the Framingham Heart Study.

Methods: We examined the second and third generations of the FHS (n= 9,219 participants) and performed linear regression analyses comparing lipid levels of mothers and fathers from Generation 2 to their offspring from Generation 3. To compare the effect of shared environment to the effect of shared genetics, we then analyzed correlation between parents from Generation 2, who were unrelated but shared a living environment. Correlations (R2) of lipid traits were computed and adjusted for BMI, age, smoking status, and menopausal status.

Results: The relationship of parent to offspring lipid traits was highly significant, even when adjusted for confounders. The relationship of parent-to-child LDL was the most significant with R2=0.089; the comparison of father to mother (parent-parent) LDL was much lower with R2=0.010.  The total variance of offspring’s HDL explained by parental HDL was 5%, while parent-to-parent comparison accounted for only 0.8% of observed variance.  As expected, triglycerides were the most variable lipid with little of the variance explained either by parent of origin or shared environment (R2 0.013 and 0.003, respectively). The p-values for each comparison were highly significant (p<1e-4) aside from parent-parent TG (p=0.449). 

Conclusions:There is a significant relationship between lipid phenotypes of parents and offspring, whereas the influence of environment is small but statistically significant. These results support a dominant role of genetics over environment in determining serum lipid levels.

1. Kathiresan S et al. A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study. BMC Med Genet. 2007; 8(Suppl 1): S17. 2. Tesolvitch et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 465, 707-713 (2010). 3. Predazzi IM et al. Parent of Origin Effect on Lipid Profiles. AHA Annual Scientific Session platform presentation, November 2012.

Nothing to Disclose: JSL, IMP, WSB, MRFL, SF, SMW

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Previous Abstract | Next Abstract >>