DNA Methylation Changes in Whole Blood and CD16+ Neutrophils in Response to Chronic Folic Acid Supplementation in Women of Childbearing Age

Abstract

Folate is a key source of one‐carbon groups for DNA methylation; but studies on DNA methylation response to folic acid (FA) supplementation show inconsistent results. We hypothesize that measuring DNA methylation in whole blood (WB), which contains a mixture of distinct leukocyte cell types, may have confounded the results of previous studies. Therefore, the aim of this pilot study was to determine if a single cell type could serve as a more reliable epigenetic reporter. The study was performed in normal weight (BMI 18.5 – 24.9 kg/m2) women (18 – 35 y; n = 12), with blood samples taken before and after eight weeks of supplementation with 800 ug/day of FA. CD16+ cells (CD16) were isolated using antibody‐bound magnetic beads. DNA methylation patterns from WB and CD16 cells were measured across >485,000 CpG sites using the Infinium Human Methylation450 Bead Chip. For each CpG site, the proportion of DNA methylation that changed over the 8 week intervention was evaluated by fitting a separate linear model. Genome‐wide analysis indicated changes in 7887 vs. 8482 CpG sites in response to supplementation in WB and CD16, respectively; with DNA methylation decreased in 77.2% (WB) or 66.3% (CD16) of these sites. Results suggest that there are differences in methylation response in WB and CD16 after FA supplementation. The implication of these methylation differences are being explored in our on‐going gene enrichment analyses. Grant Funding Source: Funded in part by HATCH #GEO00706, #GEO00707 and the Obesity Initiative at the University of Georgia

A meta-analysis of immune-cell fractions at high resolution reveals novel associations with common phenotypes and health outcomes

“…The higher NK-cell fraction in males compared to females is validated by several reports [ 50 , 65 ] and a study that used single-cell RNA sequencing to compare immune-cell fractions between males and females [ 66 ]. There is also strong prior evidence for an increased NK fraction with age [ 38 – 40 ], and in individuals undergoing frequent physical exercise [ 103 , 104 ], further validating the NK component of our reference matrix. The increased monocyte fraction in males compared to females has also been previously observed [ 105 ].…”

“…From Nestor et al [ 39 ], we obtained 8 CD4 + T-cell 450k samples (GEO: GSE50222). From Shade et al [ 40 ], we obtained 12 neutrophil 450k samples (GEO: GSE63499). From Limbach et al [ 41 ], we obtained 31 CD4 + T-cell and 31 CD8 + T-cell 450k samples (GEO: GSE71955).…”

A meta-analysis of immune cell fractions at high resolution reveals novel associations with common phenotypes and health outcomes

“…From Nestor et al [74]we obtained 8 CD4+ T-cell 450k samples (GEO: GSE50222). From Shade et al [75]we obtained 12 neutrophil 450k samples (GEO: GSE63499). From Limbach et al [76] we obtained 31 CD4+ T-cell and 31 CD8+ T-cell 450k samples (GEO: GSE71955).…”