Epigenome-wide association study of triglyceride postprandial responses to high-fat dietary challenge in the Genetics of Lipid Lowering Drugs and Diet Network study

Authors: Lai, Chao Qiang; WOJCZYNSKI, MARY - Washington University School Of Medicine; Parnell, Laurence; HIDALGO, BERTHA - University Of Alabama; IRVIN, MARGUERITE - University Of Alabama; ASLIBEKYAN, STELLA - University Of Alabama; PROVINCE, MICHAEL - Washington University School Of Medicine; DEVIN, ABSHER - Hudsonalpha Institute For Biotechnology; ARNETT, DONNA - University Of Alabama; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/16/2016
Publication Date: 10/16/2016
Citation: Lai, C., Wojczynski, M.K., Parnell, L.D., Hidalgo, B., Irvin, M.R., Aslibekyan, S., Province, M.A., Devin, A., Arnett, D.K., Ordovas, J. 2016. Epigenome-wide association study of triglyceride postprandial responses to high-fat dietary challenge in the Genetics of Lipid Lowering Drugs and Diet Network study. Journal of Lipid Research. 57:2200-2207.

Interpretive Summary: Following food consumption there is a rise in the amount of triglycerides (TG) in the blood, particularly after a fat-rich meal. This has been identified as a factor contributing to obesity and cardiovascular disease risk. Both the magnitude of the increase and the time to return to fasting levels depends, among other factors, on common genetic differences between people, but few of these genetic factors have been identified. We examined over 450,000 sites across the human genome where transient, but highly influential modifications to the DNA, so-called epigenetic marks, occur. This was done in 979 persons following the consumption of a fat-rich meal. We identified eight sites in five genes that were strongly correlated with the rise in blood TG after the fat-rich meal, revealing that these sites are major contributors to TG variation in response to food consumption. In summary, this work shows that epigenetic differences between individuals influence TG levels, an established indicator of cardiovascular disease risk. Because the epigenetic differences are potentially modifiable by diet, it is possible to develop an effective, personal strategy to reduce cardiovascular disease risk for a given individual.

Technical Abstract: Postprandial lipemia (PPL), the increased plasma triglyceride (TG) concentration after consuming a high-fat meal, is an independent risk factor for cardiovascular disease (CVD). Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few loci have been associated with TG PPL response, and most of the genetic variation remains unexplained. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study (EWAS) with 979 subjects who were challenged with a high-fat meal in the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites, encompassing five genes: LPP, CPT1A, APOA5, SREBF1, ABCG1 were significantly associated with PPL response at an epigenome-wide level (P<1.1x10-7). Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower CPT1A methylation each was correlated with an increased TG PPL response. These methylation sites account for a substantially greater amount of phenotypic variance (15.7%) in PPL when compared to the genetic contribution of loci identified by our previous genome-wide association study (4.6%). In summary, the epigenome is a large contributor to the variation in PPL, and this has potential to be exploited to modulate PPL and reduce CVD.