Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge

Chao Qiang Lai; Mary K. Wojczynski; Laurence D. Parnell; Bertha A. Hidalgo; Marguerite Ryan Irvin; Stella Aslibekyan; Michael A. Province; Devin M. Absher; Donna K. Arnett; José M. Ordovás

doi:10.1194/jlr.M069948

Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge

Chao Qiang Lai, Mary K. Wojczynski, Laurence D. Parnell, Bertha A. Hidalgo, Marguerite Ryan Irvin, Stella Aslibekyan, Michael A. Province, Devin M. Absher, Donna K. Arnett, José M. Ordovás

College of Public Health

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for 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. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4+ T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 ∼ 10^-7), but no methylation site reached epigenomewide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genomewide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD..

Original language	English
Pages (from-to)	2200-2207
Number of pages	8
Journal	Journal of Lipid Research
Volume	57
Issue number	12
DOIs	https://doi.org/10.1194/jlr.M069948
State	Published - 2016

Bibliographical note

Funding Information:
This work was funded by the U.S. Department of Agriculture under agreement number 8050-51000-098-00D and by National Heart, Lung, and Blood Institute Grant U01-HL072524-04. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Department of Agriculture. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. The USDA is an equal opportunity provider and employer.

Publisher Copyright:
Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Keywords

Apolipoproteins
Atherosclerosis
DNA methylation
Diet and dietary lipids
Dietary fat
Lipoproteins
Postprandial lipemia
Triglycerides

ASJC Scopus subject areas

Biochemistry
Endocrinology
Cell Biology

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10.1194/jlr.M069948

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@article{735d8b7335304f189b14863233fc0646,

title = "Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge",

abstract = "Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for 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. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4+ T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 ∼ 10-7), but no methylation site reached epigenomewide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genomewide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD..",

keywords = "Apolipoproteins, Atherosclerosis, DNA methylation, Diet and dietary lipids, Dietary fat, Lipoproteins, Postprandial lipemia, Triglycerides",

author = "Lai, {Chao Qiang} and Wojczynski, {Mary K.} and Parnell, {Laurence D.} and Hidalgo, {Bertha A.} and Irvin, {Marguerite Ryan} and Stella Aslibekyan and Province, {Michael A.} and Absher, {Devin M.} and Arnett, {Donna K.} and Ordov{\'a}s, {Jos{\'e} M.}",

note = "Funding Information: This work was funded by the U.S. Department of Agriculture under agreement number 8050-51000-098-00D and by National Heart, Lung, and Blood Institute Grant U01-HL072524-04. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Department of Agriculture. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. The USDA is an equal opportunity provider and employer. Publisher Copyright: Copyright {\textcopyright} 2016 by the American Society for Biochemistry and Molecular Biology, Inc.",

year = "2016",

doi = "10.1194/jlr.M069948",

language = "English",

volume = "57",

pages = "2200--2207",

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T1 - Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge

AU - Lai, Chao Qiang

AU - Wojczynski, Mary K.

AU - Parnell, Laurence D.

AU - Hidalgo, Bertha A.

AU - Irvin, Marguerite Ryan

AU - Aslibekyan, Stella

AU - Province, Michael A.

AU - Absher, Devin M.

AU - Arnett, Donna K.

AU - Ordovás, José M.

N1 - Funding Information: This work was funded by the U.S. Department of Agriculture under agreement number 8050-51000-098-00D and by National Heart, Lung, and Blood Institute Grant U01-HL072524-04. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Department of Agriculture. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. The USDA is an equal opportunity provider and employer. Publisher Copyright: Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

PY - 2016

Y1 - 2016

N2 - Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for 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. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4+ T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 ∼ 10-7), but no methylation site reached epigenomewide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genomewide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD..

AB - Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for 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. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4+ T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 ∼ 10-7), but no methylation site reached epigenomewide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genomewide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD..

KW - Apolipoproteins

KW - Atherosclerosis

KW - DNA methylation

KW - Diet and dietary lipids

KW - Dietary fat

KW - Lipoproteins

KW - Postprandial lipemia

KW - Triglycerides

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AN - SCOPUS:85002926657

SN - 0022-2275

VL - 57

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EP - 2207

JO - Journal of Lipid Research

JF - Journal of Lipid Research

IS - 12

ER -

Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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