Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis

Pooja R. Mandaviya; Dylan Aissi; Koen F. Dekkers; Roby Joehanes; Silva Kasela; Vinh Truong; Lisette Stolk; Diana van Heemst; M. Arfan Ikram; Jan Lindemans; P. Eline Slagboom; David-Alexandre Tregouet; Andre G. Uitterlinden; Chen Wei; Phil Wells; France Gagnon; Marleen M. J. van Greevenbroek; Bastiaan T. Heijmans; Lili Milani; Pierre-Emmanuel Morange; Joyce B. J. van Meurs; Sandra G. Heil; BIOS Consortium

doi:10.2217/epi-2017-0038

Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis

Pooja R. Mandaviya
, Dylan Aissi
, Koen F. Dekkers
, Roby Joehanes
, Silva Kasela
, Vinh Truong
, Lisette Stolk
, Diana van Heemst
, M. Arfan Ikram
, Jan Lindemans
, P. Eline Slagboom
, David-Alexandre Tregouet
, Andre G. Uitterlinden
, Chen Wei
, Phil Wells
, France Gagnon
, Marleen M. J. van Greevenbroek
, Bastiaan T. Heijmans
, Lili Milani
, Pierre-Emmanuel Morange

Joyce B. J. van Meurs, Sandra G. Heil^*, BIOS Consortium

^*Corresponding author for this work

Interne Geneeskunde

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

Abstract

Aim: Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes. Methods: Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis. Results: Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy. In addition, we identified 68 Hcy-associated differentially methylated regions, the most significant of which was a 1.8-kb spanning domain (TNXB/ATF6B) at chromosome 6. Conclusion: We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated.

Original language	English
Pages (from-to)	1403-1422
Number of pages	20
Journal	Epigenomics
Volume	9
Issue number	11
DOIs	https://doi.org/10.2217/epi-2017-0038
Publication status	Published - Nov 2017

Keywords

450 k array
association
DMP
DMR
DNA methylation
epigenome-wide analysis
homocysteine
meta-analysis
RANDOMIZED CONTROLLED-TRIAL
ESTROGEN-RECEPTOR-ALPHA
SMOOTH-MUSCLE-CELLS
PLASMA HOMOCYSTEINE
S-ADENOSYLHOMOCYSTEINE
GENOME-WIDE
FOLIC-ACID
VASCULAR-DISEASE
LIM PROTEIN
MYOCARDIAL-INFARCTION

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https://pure.eur.nl/en/publications/5412975d-1f97-4d5b-a03b-9cf4557679b4Licence: Other

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Mandaviya, P. R., Aissi, D., Dekkers, K. F., Joehanes, R., Kasela, S., Vinh Truong, Stolk, L., van Heemst, D., Ikram, M. A., Lindemans, J., Slagboom, P. E., Tregouet, D.-A., Uitterlinden, A. G., Wei, C., Wells, P., Gagnon, F., van Greevenbroek, M. M. J., Heijmans, B. T., Milani, L., ... BIOS Consortium (2017). Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis. Epigenomics, 9(11), 1403-1422. https://doi.org/10.2217/epi-2017-0038

@article{7cbe55500f144d0c91d5bab30f01aa27,

title = "Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis",

abstract = "Aim: Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes. Methods: Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis. Results: Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy. In addition, we identified 68 Hcy-associated differentially methylated regions, the most significant of which was a 1.8-kb spanning domain (TNXB/ATF6B) at chromosome 6. Conclusion: We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated.",

keywords = "450 k array, association, DMP, DMR, DNA methylation, epigenome-wide analysis, homocysteine, meta-analysis, RANDOMIZED CONTROLLED-TRIAL, ESTROGEN-RECEPTOR-ALPHA, SMOOTH-MUSCLE-CELLS, PLASMA HOMOCYSTEINE, S-ADENOSYLHOMOCYSTEINE, GENOME-WIDE, FOLIC-ACID, VASCULAR-DISEASE, LIM PROTEIN, MYOCARDIAL-INFARCTION",

author = "Mandaviya, \{Pooja R.\} and Dylan Aissi and Dekkers, \{Koen F.\} and Roby Joehanes and Silva Kasela and \{Vinh Truong\} and Lisette Stolk and \{van Heemst\}, Diana and Ikram, \{M. Arfan\} and Jan Lindemans and Slagboom, \{P. Eline\} and David-Alexandre Tregouet and Uitterlinden, \{Andre G.\} and Chen Wei and Phil Wells and France Gagnon and \{van Greevenbroek\}, \{Marleen M. J.\} and Heijmans, \{Bastiaan T.\} and Lili Milani and Pierre-Emmanuel Morange and \{van Meurs\}, \{Joyce B. J.\} and Heil, \{Sandra G.\} and \{BIOS Consortium\}",

year = "2017",

month = nov,

doi = "10.2217/epi-2017-0038",

language = "English",

volume = "9",

pages = "1403--1422",

journal = "Epigenomics",

issn = "1750-1911",

publisher = "Routledge/Taylor \& Francis Group",

number = "11",

}

Mandaviya, PR, Aissi, D, Dekkers, KF, Joehanes, R, Kasela, S, Vinh Truong, Stolk, L, van Heemst, D, Ikram, MA, Lindemans, J, Slagboom, PE, Tregouet, D-A, Uitterlinden, AG, Wei, C, Wells, P, Gagnon, F, van Greevenbroek, MMJ, Heijmans, BT, Milani, L, Morange, P-E, van Meurs, JBJ, Heil, SG & BIOS Consortium 2017, 'Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis', Epigenomics, vol. 9, no. 11, pp. 1403-1422. https://doi.org/10.2217/epi-2017-0038

TY - JOUR

T1 - Homocysteine levels associate with subtle changes in leukocyte DNA methylation

T2 - an epigenome-wide analysis

AU - Mandaviya, Pooja R.

AU - Aissi, Dylan

AU - Dekkers, Koen F.

AU - Joehanes, Roby

AU - Kasela, Silva

AU - Vinh Truong, null

AU - Stolk, Lisette

AU - van Heemst, Diana

AU - Ikram, M. Arfan

AU - Lindemans, Jan

AU - Slagboom, P. Eline

AU - Tregouet, David-Alexandre

AU - Uitterlinden, Andre G.

AU - Wei, Chen

AU - Wells, Phil

AU - Gagnon, France

AU - van Greevenbroek, Marleen M. J.

AU - Heijmans, Bastiaan T.

AU - Milani, Lili

AU - Morange, Pierre-Emmanuel

AU - van Meurs, Joyce B. J.

AU - Heil, Sandra G.

AU - BIOS Consortium

PY - 2017/11

Y1 - 2017/11

N2 - Aim: Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes. Methods: Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis. Results: Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy. In addition, we identified 68 Hcy-associated differentially methylated regions, the most significant of which was a 1.8-kb spanning domain (TNXB/ATF6B) at chromosome 6. Conclusion: We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated.

AB - Aim: Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes. Methods: Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis. Results: Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy. In addition, we identified 68 Hcy-associated differentially methylated regions, the most significant of which was a 1.8-kb spanning domain (TNXB/ATF6B) at chromosome 6. Conclusion: We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated.

KW - 450 k array

KW - association

KW - DMP

KW - DMR

KW - DNA methylation

KW - epigenome-wide analysis

KW - homocysteine

KW - meta-analysis

KW - RANDOMIZED CONTROLLED-TRIAL

KW - ESTROGEN-RECEPTOR-ALPHA

KW - SMOOTH-MUSCLE-CELLS

KW - PLASMA HOMOCYSTEINE

KW - S-ADENOSYLHOMOCYSTEINE

KW - GENOME-WIDE

KW - FOLIC-ACID

KW - VASCULAR-DISEASE

KW - LIM PROTEIN

KW - MYOCARDIAL-INFARCTION

U2 - 10.2217/epi-2017-0038

DO - 10.2217/epi-2017-0038

M3 - Article

C2 - 28990796

SN - 1750-1911

VL - 9

SP - 1403

EP - 1422

JO - Epigenomics

JF - Epigenomics

IS - 11

ER -

Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis

Abstract

Keywords

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