Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference

Stella Aslibekyan; Ellen W. Demerath; Michael Mendelson; Degui Zhi; Weihua Guan; Liming Liang; Jin Sha; James S. Pankow; Chunyu Liu; Marguerite R. Irvin; Myriam Fornage; Bertha Hidalgo; Li An Lin; Krista Stanton Thibeault; Jan Bressler; Michael Y. Tsai; Megan L. Grove; Paul N. Hopkins; Eric Boerwinkle; Ingrid B. Borecki; Jose M. Ordovas; Daniel Levy; Hemant K. Tiwari; Devin M. Absher; Donna K. Arnett

doi:10.1002/oby.21111

Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference

Stella Aslibekyan, Ellen W. Demerath, Michael Mendelson, Degui Zhi, Weihua Guan, Liming Liang, Jin Sha, James S. Pankow, Chunyu Liu, Marguerite R. Irvin, Myriam Fornage, Bertha Hidalgo, Li An Lin, Krista Stanton Thibeault, Jan Bressler, Michael Y. Tsai, Megan L. Grove, Paul N. Hopkins, Eric Boerwinkle, Ingrid B. BoreckiJose M. Ordovas, Daniel Levy, Hemant K. Tiwari, Devin M. Absher, Donna K. Arnett

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

146 Scopus citations

Abstract

Objective To conduct an epigenome-wide analysis of DNA methylation and obesity traits. Methods DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled. Results Epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n-=-2,377) and the Atherosclerosis Risk in Communities study (n-=-2,097), were found. Top findings were in CPT1A (meta-analysis P-=-2.7 × 10^-43 for BMI and 9.9 × 10^-23 for WC), PHGDH (meta-analysis P-=-2.0 × 10^-15 for BMI and 4.0 × 10^-9 for WC), CD38 (meta-analysis P-=-6.3 × 10^-11 for BMI and 1.6 × 10^-12 for WC), and long intergenic non-coding RNA 00263 (meta-analysis P-=-2.2 × 10^-16 for BMI and 8.9 × 10^-14 for WC), regions with biologically plausible relationships to adiposity. Conclusions This large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications.

Original language	English
Pages (from-to)	1493-1501
Number of pages	9
Journal	Obesity
Volume	23
Issue number	7
DOIs	https://doi.org/10.1002/oby.21111
State	Published - Jul 1 2015

Bibliographical note

Publisher Copyright:
© 2015 The Obesity Society.

Funding

Funders	Funder number
National Human Genome Research Institute	U01HG004402
National Institutes of Health (NIH)	HHSN268200625226C
National Center for Research Resources	UL1RR025005

ASJC Scopus subject areas

Medicine (miscellaneous)
Endocrinology, Diabetes and Metabolism
Endocrinology
Nutrition and Dietetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/oby.21111

Cite this

Aslibekyan, S., Demerath, E. W., Mendelson, M., Zhi, D., Guan, W., Liang, L., Sha, J., Pankow, J. S., Liu, C., Irvin, M. R., Fornage, M., Hidalgo, B., Lin, L. A., Stanton Thibeault, K., Bressler, J., Tsai, M. Y., Grove, M. L., Hopkins, P. N., Boerwinkle, E., ... Arnett, D. K. (2015). Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference. Obesity, 23(7), 1493-1501. https://doi.org/10.1002/oby.21111

@article{4f87254f6fd44694b5c2fcd866f311a6,

title = "Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference",

abstract = "Objective To conduct an epigenome-wide analysis of DNA methylation and obesity traits. Methods DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled. Results Epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n-=-2,377) and the Atherosclerosis Risk in Communities study (n-=-2,097), were found. Top findings were in CPT1A (meta-analysis P-=-2.7 × 10-43 for BMI and 9.9 × 10-23 for WC), PHGDH (meta-analysis P-=-2.0 × 10-15 for BMI and 4.0 × 10-9 for WC), CD38 (meta-analysis P-=-6.3 × 10-11 for BMI and 1.6 × 10-12 for WC), and long intergenic non-coding RNA 00263 (meta-analysis P-=-2.2 × 10-16 for BMI and 8.9 × 10-14 for WC), regions with biologically plausible relationships to adiposity. Conclusions This large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications.",

author = "Stella Aslibekyan and Demerath, {Ellen W.} and Michael Mendelson and Degui Zhi and Weihua Guan and Liming Liang and Jin Sha and Pankow, {James S.} and Chunyu Liu and Irvin, {Marguerite R.} and Myriam Fornage and Bertha Hidalgo and Lin, {Li An} and {Stanton Thibeault}, Krista and Jan Bressler and Tsai, {Michael Y.} and Grove, {Megan L.} and Hopkins, {Paul N.} and Eric Boerwinkle and Borecki, {Ingrid B.} and Ordovas, {Jose M.} and Daniel Levy and Tiwari, {Hemant K.} and Absher, {Devin M.} and Arnett, {Donna K.}",

note = "Publisher Copyright: {\textcopyright} 2015 The Obesity Society.",

year = "2015",

month = jul,

day = "1",

doi = "10.1002/oby.21111",

language = "English",

volume = "23",

pages = "1493--1501",

number = "7",

}

Aslibekyan, S, Demerath, EW, Mendelson, M, Zhi, D, Guan, W, Liang, L, Sha, J, Pankow, JS, Liu, C, Irvin, MR, Fornage, M, Hidalgo, B, Lin, LA, Stanton Thibeault, K, Bressler, J, Tsai, MY, Grove, ML, Hopkins, PN, Boerwinkle, E, Borecki, IB, Ordovas, JM, Levy, D, Tiwari, HK, Absher, DM & Arnett, DK 2015, 'Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference', Obesity, vol. 23, no. 7, pp. 1493-1501. https://doi.org/10.1002/oby.21111

TY - JOUR

T1 - Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference

AU - Aslibekyan, Stella

AU - Demerath, Ellen W.

AU - Mendelson, Michael

AU - Zhi, Degui

AU - Guan, Weihua

AU - Liang, Liming

AU - Sha, Jin

AU - Pankow, James S.

AU - Liu, Chunyu

AU - Irvin, Marguerite R.

AU - Fornage, Myriam

AU - Hidalgo, Bertha

AU - Lin, Li An

AU - Stanton Thibeault, Krista

AU - Bressler, Jan

AU - Tsai, Michael Y.

AU - Grove, Megan L.

AU - Hopkins, Paul N.

AU - Boerwinkle, Eric

AU - Borecki, Ingrid B.

AU - Ordovas, Jose M.

AU - Levy, Daniel

AU - Tiwari, Hemant K.

AU - Absher, Devin M.

AU - Arnett, Donna K.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Objective To conduct an epigenome-wide analysis of DNA methylation and obesity traits. Methods DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled. Results Epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n-=-2,377) and the Atherosclerosis Risk in Communities study (n-=-2,097), were found. Top findings were in CPT1A (meta-analysis P-=-2.7 × 10-43 for BMI and 9.9 × 10-23 for WC), PHGDH (meta-analysis P-=-2.0 × 10-15 for BMI and 4.0 × 10-9 for WC), CD38 (meta-analysis P-=-6.3 × 10-11 for BMI and 1.6 × 10-12 for WC), and long intergenic non-coding RNA 00263 (meta-analysis P-=-2.2 × 10-16 for BMI and 8.9 × 10-14 for WC), regions with biologically plausible relationships to adiposity. Conclusions This large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications.

AB - Objective To conduct an epigenome-wide analysis of DNA methylation and obesity traits. Methods DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled. Results Epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n-=-2,377) and the Atherosclerosis Risk in Communities study (n-=-2,097), were found. Top findings were in CPT1A (meta-analysis P-=-2.7 × 10-43 for BMI and 9.9 × 10-23 for WC), PHGDH (meta-analysis P-=-2.0 × 10-15 for BMI and 4.0 × 10-9 for WC), CD38 (meta-analysis P-=-6.3 × 10-11 for BMI and 1.6 × 10-12 for WC), and long intergenic non-coding RNA 00263 (meta-analysis P-=-2.2 × 10-16 for BMI and 8.9 × 10-14 for WC), regions with biologically plausible relationships to adiposity. Conclusions This large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications.

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DO - 10.1002/oby.21111

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VL - 23

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JO - Obesity

JF - Obesity

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Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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