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; null 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 MorangeJoyce 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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10.2217/epi-2017-0038

Cite this

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 = "Future Medicine Ltd.",

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 -