TY  - JOUR
AB  - BACKGROUND: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. CONCLUSIONS: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.
AU  - Keshawarz, A.*
AU  - Joehanes, R.*
AU  - Ma, J.*
AU  - Lee, G.Y.*
AU  - Costeira, R.*
AU  - Tsai, P.C.*
AU  - Masachs, O.M.*
AU  - Bell, J.T.*
AU  - Wilson, R.
AU  - Thorand, B.
AU  - Winkelmann, J.
AU  - Peters, A.
AU  - Linseisen, J.*
AU  - Waldenberger, M.
AU  - Lehtimäki, T.*
AU  - Mishra, P.P.*
AU  - Kähönen, M.*
AU  - Raitakari, O.*
AU  - Helminen, M.*
AU  - Wang, C.A.*
AU  - Melton, P.E.*
AU  - Huang, R.C.*
AU  - Pennell, C.E.*
AU  - O'Sullivan, T.A.*
AU  - Ochoa-Rosales, C.*
AU  - Voortman, T.*
AU  - van Meurs, J.B.J.*
AU  - Young, K.L.*
AU  - Graff, M.*
AU  - Wang, Y.*
AU  - Kiel, D.P.*
AU  - Smith, C.E.*
AU  - Jacques, P.F.*
AU  - Levy, D.*
C1  - 67888
C2  - 54366
CY  - 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
TI  - Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis.
JO  - Epigenetics
VL  - 18
IS  - 1
PB  - Taylor & Francis Inc
PY  - 2023
SN  - 1559-2294
ER  - 

TY  - JOUR
AB  - Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.
AU  - Ronkainen, J.*
AU  - Heiskala, A.*
AU  - Vehmeijer, F.O.L.*
AU  - Lowry, E.*
AU  - Caramaschi, D.*
AU  - Estrada Gutierrez, G.*
AU  - Heiss, J.A.*
AU  - Hummel, N.
AU  - Keikkala, E.*
AU  - Kvist, T.*
AU  - Kupsco, A.*
AU  - Melton, P.E.*
AU  - Pesce, G.*
AU  - Soomro, M.H.*
AU  - Vives-Usano, M.*
AU  - Baïz, N.*
AU  - Binder, E.*
AU  - Czamara, D.*
AU  - Guxens, M.*
AU  - Mustaniemi, S.*
AU  - London, S.J.*
AU  - Rauschert, S.*
AU  - Vääräsmäki, M.*
AU  - Vrijheid, M.*
AU  - Ziegler, A.G.*
AU  - Annesi-Maesano, I.*
AU  - Bustamante, M.*
AU  - Huang, R.C.*
AU  - Hummel, S.*
AU  - Just, A.C.*
AU  - Kajantie, E.*
AU  - Lahti, J.*
AU  - Lawlor, D.*
AU  - Räikkönen, K.*
AU  - Järvelin, M.R.*
AU  - Felix, J.F.*
AU  - Sebert, S.*
C1  - 60972
C2  - 50003
CY  - 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
SP  - 19-31
TI  - Maternal haemoglobin levels in pregnancy and child DNA methylation: A study in the pregnancy and childhood epigenetics consortium.
JO  - Epigenetics
VL  - 17
IS  - 1
PB  - Taylor & Francis Inc
PY  - 2022
SN  - 1559-2294
ER  - 

TY  - JOUR
AB  - DNA methylation is an epigenetic regulator of gene transcription, which has been found to be both metastable and variable within human cohort studies. Currently, few studies have been done to identify metastable DNA methylation biomarkers associated with longitudinal lung function decline in humans. The identification of such biomarkers is important for screening vulnerable populations. We hypothesized that quantifiable blood-based DNA methylation alterations would serve as metastable biomarkers of lung function decline and aging, which may help to discover new pathways and/or mechanisms related to pulmonary pathogenesis. Using linear mixed models, we performed an Epigenome Wide Association Study (EWAS) between DNA methylation at CpG dinucleotides and longitudinal lung function (FVC, FEV1, FEF25-75%) decline and aging with initial discovery in the Normative Aging Study, and replication in the Cooperative Health Research in the Region of Augsburg cohort. We identified two metastable epigenetic loci associated with either poor lung function and aging, cg05575921 (AHRR gene), or lung function independently of aging, cg06126421 (IER3 gene). These loci may inform basic mechanisms associated with pulmonary function, pathogenesis, and aging. Human epigenomic variation, may help explain features of lung function decline and related pathophysiology not attributable to DNA sequence alone, such as accelerated pulmonary decline in smokers, former smokers, and perhaps non-smokers. Our EWAS across two cohorts, therefore, will likely have implications for the human population, not just the elderly.
AU  - Carmona, J.J.*
AU  - Barfield, R.T.*
AU  - Panni, T.
AU  - Nwanaji-Enwerem, J.C.*
AU  - Just, A.C.*
AU  - Hutchinson, J.N.*
AU  - Colicino, E.*
AU  - Karrasch, S.
AU  - Wahl, S.
AU  - Kunze, S.
AU  - Jafari, N.*
AU  - Zheng, Y.*
AU  - Hou, L.*
AU  - DeMeo, D.L.*
AU  - Litonjua, A.A.*
AU  - Vokonas, P.S.*
AU  - Peters, A.
AU  - Lin, X.*
AU  - Schwartz, J.*
AU  - Schulz, H.
AU  - Baccarelli, A.A.*
C1  - 54579
C2  - 45675
CY  - 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
SP  - 1039-1055
TI  - Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans: An epigenome-wide study in the NAS and KORA cohorts.
JO  - Epigenetics
VL  - 13
IS  - 10-11
PB  - Taylor & Francis Inc
PY  - 2018
SN  - 1559-2294
ER  - 

TY  - JOUR
AB  - An intense period of chromatin remodeling takes place after fertilization in mammals, which is thought necessary for epigenetic reprogramming to start a new developmental program. While much attention has been given to the role of Polycomb Repressive Complex 2 (PRC2) and to canonical PRC1 complexes during this process, little is known as to whether there is any contribution of non-canonical PRC1 in shaping the chromatin landscape after fertilization. Here, we first describe in detail the temporal dynamics and abundance of H2A ubiquitylation (H2AK119ub), a histone modification catalyzed by PRC1, during pre-implantation mouse development. In addition, we have analyzed the presence of the 2 characteristic subunits of non-canonical PRC1 complexes, RYBP and its homolog YAF-2. Our results indicate that H2AK119ub is inherited from the sperm, rapidly removed from the paternal chromatin after fertilization, but detected again prior to the first mitosis, suggesting that PRC1 activity occurs as early as the zygotic stage. RYBP and YAF-2, together with the non-canonical subunit L3MBTL2, are all present during pre-implantation development but show different temporal dynamics. While RYBP is absent in the zygote, it is strongly induced from the 4-cell stage onwards. YAF-2 is inherited maternally and localizes to the pericentromeric regions in the zygote, is strongly induced between the 2- and 4-cell stages but then remains weak to undetectable subsequently. All together, our data suggest that non-canonical PRC1 is active during pre-implantation development and should be regarded as an additional component during epigenetic reprogramming and in the establishment of cellular plasticity of the early embryo.
AU  - Eid, A.*
AU  - Torres-Padilla, M.E.
C1  - 48635
C2  - 41233
CY  - Philadelphia
SP  - 389-397
TI  - Characterization of non-canonical polycomb repressive complex 1 subunits during early mouse embryogenesis.
JO  - Epigenetics
VL  - 11
IS  - 6
PB  - Taylor & Francis Inc
PY  - 2016
SN  - 1559-2294
ER  - 

TY  - JOUR
AB  - Aberrant DNA methylation is a major epigenetic mechanism of gene silencing in a wide range of human cancers. Previous studies on DNA methylation typically used paired tumor and normal-appearing surrounding tissues from cancer-bearing individuals. However, genomic DNA isolated from surrogate tissues such as blood cells represents an attractive material that can be exploited in the discovery of biomarkers of exposure and tumorigenesis. Here we examined the association between lung cancer and DNA methylation patterns in a panel of candidate genes. We also investigated whether blood levels of vitamin metabolites modify DNA methylation levels in blood cells. To this end, we quantitatively determined DNA methylation levels in blood cells of nested cases and controls from a prospective study with well defined dietary habits and lifestyles. Multiple CpG sites in five genes (CDKN2A/p16, RASSF1A, GSTP1, MTHFR, and MGMT) that are frequent targets of hypermethylation in a variety of human malignancies were included in the analysis. While no clear association between DNA methylation patterns and the case/control status was found, with the exception of RASSF1A hypermethylation, methylation level changed according to serum levels of 1-carbon metabolites and vitamins B. Overall, folate was associated with increased methylation levels of RASSF1A and MTHFR and methionine was associated with decreased methylation levels of RASSF1A. The associations with folate were more pronounced among never smokers while the associations with methionine were more evident among ever-smokers. These results are consistent with the notion that blood levels of 1-carbon metabolism markers and dietary/lifestyle factors may modify DNA methylation levels in blood cells and that blood cells can be exploited for the discovery of epigenetic biomarkers of exposures, providing proof-of-principle on the use of blood samples in the context of prospective studies.
AU  - Vineis, P.*
AU  - Chuang, S.C.*
AU  - Vaissière, T.*
AU  - Cuenin, C.*
AU  - Ricceri, F*
AU  - Genair-EPIC Collaborators (Linseisen, J.)
AU  - Johansson, M.*
AU  - Ueland, P.*
AU  - Brennan, P.*
AU  - Herceg, Z.*
C1  - 6504
C2  - 28823
CY  - Austin, TX, USA
SP  - 195-201
TI  - DNA methylation changes associated with cancer risk factors and blood levels of vitamin metabolites in a prospective study.
JO  - Epigenetics
VL  - 6
IS  - 2
PB  - Landes Bioscience
PY  - 2011
SN  - 1559-2294
ER  -