Association of DNA methylation at CPT1A locus with metabolic syndrome in the genetics of lipid lowering drugs and diet network (GOLDN) study

Mithun Das; Jin Sha; Bertha Hidalgo; Stella Aslibekyan; Anh N. Do; Degui Zhi; Dianjianyi Sun; Tao Zhang; Shengxu Li; Wei Chen; Sathanur R. Srinivasan; Hemant K. Tiwari; Devin Absher; Jose M. Ordovas; Gerald S. Berenson; Donna K. Arnett; Marguerite R. Irvin

doi:10.1371/journal.pone.0145789

Association of DNA methylation at CPT1A locus with metabolic syndrome in the genetics of lipid lowering drugs and diet network (GOLDN) study

Mithun Das
, Jin Sha
, Bertha Hidalgo
, Stella Aslibekyan
, Anh N. Do
, Degui Zhi
, Dianjianyi Sun
, Tao Zhang
, Shengxu Li
, Wei Chen
, Sathanur R. Srinivasan
, Hemant K. Tiwari
, Devin Absher
, Jose M. Ordovas
, Gerald S. Berenson
, Donna K. Arnett
, Marguerite R. Irvin

College of Public Health

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

59 Scopus citations

Abstract

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ∼470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 × 10^-7 was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6 × 10^-14 and P for cg17058475 = 1.2 × 10^-9). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.

Original language	English
Article number	e0145789
Journal	PLoS ONE
Volume	11
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0145789
State	Published - Jan 2016

Bibliographical note

Publisher Copyright:
© 2016 Das et al.

Funding

Funding: The GOLDN study (DKA) was funded by the US National Institutes of Health (NIH)/National Heart, Lung and Blood Institutes (http://www.nhlbi.nih. The GOLDN study (DKA) was funded by the US National Institutes of Health (NIH)/National Heart, Lung and Blood Institutes (http://www.nhlbi.nih. gov) grants R01HL104135 and U01HL72524. The Bogalusa Heart Study (GSB) was supported by grants R01AG016592 from the National Institute on Aging (https://www.nia.nih.gov) and R01ES021724 from National Institute of Environmental Health Science (http://www.niehs.nih.gov). No individuals employed or contracted by the funders played any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funders	Funder number
National Institute of Environmental Health Science
US National Institutes for Health
National Institutes of Health (NIH)
National Institute on Aging	R01AG016592, R01ES021724
National Institute on Aging
National Heart, Lung, and Blood Institute (NHLBI)	U01HL72524, R01HL104135
National Heart, Lung, and Blood Institute (NHLBI)

ASJC Scopus subject areas

General

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10.1371/journal.pone.0145789

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Das, M., Sha, J., Hidalgo, B., Aslibekyan, S., Do, A. N., Zhi, D., Sun, D., Zhang, T., Li, S., Chen, W., Srinivasan, S. R., Tiwari, H. K., Absher, D., Ordovas, J. M., Berenson, G. S., Arnett, D. K., & Irvin, M. R. (2016). Association of DNA methylation at CPT1A locus with metabolic syndrome in the genetics of lipid lowering drugs and diet network (GOLDN) study. PLoS ONE, 11(1), Article e0145789. https://doi.org/10.1371/journal.pone.0145789

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title = "Association of DNA methylation at CPT1A locus with metabolic syndrome in the genetics of lipid lowering drugs and diet network (GOLDN) study",

abstract = "In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ∼470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 {\texttimes} 10-7 was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6 {\texttimes} 10-14 and P for cg17058475 = 1.2 {\texttimes} 10-9). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.",

author = "Mithun Das and Jin Sha and Bertha Hidalgo and Stella Aslibekyan and Do, \{Anh N.\} and Degui Zhi and Dianjianyi Sun and Tao Zhang and Shengxu Li and Wei Chen and Srinivasan, \{Sathanur R.\} and Tiwari, \{Hemant K.\} and Devin Absher and Ordovas, \{Jose M.\} and Berenson, \{Gerald S.\} and Arnett, \{Donna K.\} and Irvin, \{Marguerite R.\}",

note = "Publisher Copyright: {\textcopyright} 2016 Das et al.",

year = "2016",

month = jan,

doi = "10.1371/journal.pone.0145789",

language = "English",

volume = "11",

number = "1",

}

Das, M, Sha, J, Hidalgo, B, Aslibekyan, S, Do, AN, Zhi, D, Sun, D, Zhang, T, Li, S, Chen, W, Srinivasan, SR, Tiwari, HK, Absher, D, Ordovas, JM, Berenson, GS, Arnett, DK & Irvin, MR 2016, 'Association of DNA methylation at CPT1A locus with metabolic syndrome in the genetics of lipid lowering drugs and diet network (GOLDN) study', PLoS ONE, vol. 11, no. 1, e0145789. https://doi.org/10.1371/journal.pone.0145789

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T1 - Association of DNA methylation at CPT1A locus with metabolic syndrome in the genetics of lipid lowering drugs and diet network (GOLDN) study

AU - Das, Mithun

AU - Sha, Jin

AU - Hidalgo, Bertha

AU - Aslibekyan, Stella

AU - Do, Anh N.

AU - Zhi, Degui

AU - Sun, Dianjianyi

AU - Zhang, Tao

AU - Li, Shengxu

AU - Chen, Wei

AU - Srinivasan, Sathanur R.

AU - Tiwari, Hemant K.

AU - Absher, Devin

AU - Ordovas, Jose M.

AU - Berenson, Gerald S.

AU - Arnett, Donna K.

AU - Irvin, Marguerite R.

PY - 2016/1

Y1 - 2016/1

N2 - In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ∼470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 × 10-7 was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6 × 10-14 and P for cg17058475 = 1.2 × 10-9). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.

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Association of DNA methylation at CPT1A locus with metabolic syndrome in the genetics of lipid lowering drugs and diet network (GOLDN) study

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

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