Dataset Information

Tobacco exposure-related alterations in DNA methylation and gene expression in human monocytes: the Multi-Ethnic Study of Atherosclerosis (MESA).

ABSTRACT: Alterations in DNA methylation and gene expression in blood leukocytes are potential biomarkers of harm and mediators of the deleterious effects of tobacco exposure. However, methodological issues, including the use of self-reported smoking status and mixed cell types have made previously identified alterations in DNA methylation and gene expression difficult to interpret. In this study, we examined associations of tobacco exposure with DNA methylation and gene expression, utilizing a biomarker of tobacco exposure (urine cotinine) and CD14+ purified monocyte samples from 934 participants of the community-based Multi-Ethnic Study of Atherosclerosis (MESA). Urine cotinine levels were measured using an immunoassay. DNA methylation and gene expression were measured with microarrays. Multivariate linear regression was used to test for associations adjusting for age, sex, race/ethnicity, education, and study site. Urine cotinine levels were associated with methylation of 176 CpGs [false discovery rate (FDR)<0.01]. Four CpGs not previously identified by studies of non-purified blood samples nominally replicated (P value<0.05) with plasma cotinine-associated methylation in 128 independent monocyte samples. Urine cotinine levels associated with expression of 12 genes (FDR<0.01), including increased expression of P2RY6 (Beta ± standard error = 0.078 ± 0.008, P = 1.99 × 10^-22), a gene previously identified to be involved in the release of pro-inflammatory cytokines. No cotinine-associated (FDR<0.01) methylation profiles significantly (FDR<0.01) correlated with cotinine-associated (FDR<0.01) gene expression profiles. In conclusion, our findings i) identify potential monocyte-specific smoking-associated methylation patterns and ii) suggest that alterations in methylation may not be a main mechanism regulating gene expression in monocytes in response to cigarette smoking.

SUBMITTER: Reynolds LM

PROVIDER: S-EPMC5810757 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tobacco exposure-related alterations in DNA methylation and gene expression in human monocytes: the Multi-Ethnic Study of Atherosclerosis (MESA).

Reynolds Lindsay M LM Lohman Kurt K Pittman Gary S GS Barr R Graham RG Chi Gloria C GC Kaufman Joel J Wan Ma M Bell Douglas A DA Blaha Michael J MJ Rodriguez Carlos J CJ Liu Yongmei Y

Epigenetics 20170101 12

Alterations in DNA methylation and gene expression in blood leukocytes are potential biomarkers of harm and mediators of the deleterious effects of tobacco exposure. However, methodological issues, including the use of self-reported smoking status and mixed cell types have made previously identified alterations in DNA methylation and gene expression difficult to interpret. In this study, we examined associations of tobacco exposure with DNA methylation and gene expression, utilizing a biomarker ...[more]

PMID: 29166816

Similar Datasets

Project description:DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ?55).One-year average ambient fine particulate matter (PM2.5) and oxides of nitrogen (NOX) concentrations were predicted at participants' (n?=?1,207) addresses using spatiotemporal models. We assessed DNA methylation in circulating monocytes at 1) 2,713 CpG sites associated with mRNA expression of nearby genes and 2) probes mapping to Alu and LINE-1 repetitive elements (surrogates for global DNA methylation) using Illumina's Infinium HumanMethylation450 BeadChip. We used linear regression models adjusted for demographics, smoking, physical activity, socioeconomic status, methyl-nutrients, and technical variables. For significant air pollution-associated methylation sites, we also assessed the association between expression of gene transcripts previously associated with these CpG sites and air pollution.At a false discovery rate of 0.05, five candidate CpGs (cg20455854, cg07855639, cg07598385, cg17360854, and cg23599683) had methylation significantly associated with PM2.5 and none were associated with NOX. Cg20455854 had the smallest p-value for the association with PM2.5 (p?=?2.77?×?10-5). mRNA expression profiles of genes near three of the PM2.5-associated CpGs (ANKHD1, LGALS2, and ANKRD11) were also significantly associated with PM2.5 exposure. Alu and LINE-1 methylation were not associated with long-term air pollution exposure.We observed novel associations between long-term ambient air pollution exposure and site-specific DNA methylation, but not global DNA methylation, in purified monocytes of a multi-ethnic adult population. Epigenetic markers may provide insights into mechanisms underlying environmental factors in complex diseases like atherosclerosis.

Project description:Air pollution might affect atherosclerosis through DNA methylation changes in cells crucial to atherosclerosis, such as monocytes. We conducted an epigenome-wide study of DNA methylation in CD14+ monocytes and long-term ambient air pollution exposure in adults participating in the Multi-Ethnic Study of Atherosclerosis (MESA). We also assessed the association between differentially methylated signals and cis-gene expression. Using spatiotemporal models, one-year average concentrations of outdoor fine particulate matter (PM2.5) and oxides of nitrogen (NOX) were estimated at participants' homes. We assessed DNA methylation and gene expression using Illumina 450k and HumanHT-12 v4 Expression BeadChips, respectively (n = 1,207). We used bump hunting and site-specific approaches to identify differentially methylated signals (false discovery rate of 0.05) and used linear models to assess associations between differentially methylated signals and cis-gene expression. Four differentially methylated regions (DMRs) located on chromosomes 5, 6, 7, and 16 (within or near SDHAP3, ZFP57, HOXA5, and PRM1, respectively) were associated with PM2.5. The DMRs on chromosomes 5 and 6 also associated with NOX. The DMR on chromosome 5 had the smallest p-value for both PM2.5 (p = 1.4×10-6) and NOX (p = 7.7×10-6). Three differentially methylated CpGs were identified for PM2.5, and cg05926640 (near TOMM20) had the smallest p-value (p = 5.6×10-8). NOX significantly associated with cg11756214 within ZNF347 (p = 5.6×10-8). Several differentially methylated signals were also associated with cis-gene expression. The DMR located on chromosome 7 was associated with the expression of HOXA5, HOXA9, and HOXA10. The DMRs located on chromosomes 5 and 16 were associated with expression of MRPL36 and DEXI, respectively. The CpG cg05926640 was associated with expression of ARID4B, IRF2BP2, and TOMM20. We identified differential DNA methylation in monocytes associated with long-term air pollution exposure. Methylation signals associated with gene expression might help explain how air pollution contributes to cardiovascular disease.

Project description:ObjectiveExposure to light at night (LAN) may influence sleep timing and regularity. Here, we test whether greater light exposure during sleep (LEDS) associates with greater irregularity in sleep onset timing in a large cohort of older adults.MethodsLight exposure and activity patterns, measured via wrist-worn actigraphy (ActiWatch Spectrum), were analyzed in 1,933 participants with 6+ valid days of data in the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 5 Sleep Study. Summary measures of LEDS averaged across nights were evaluated in linear and logistic regression analyses to test the association with standard deviation (SD) in sleep onset timing (continuous variable) and irregular sleep onset timing (SD≥1.36 hours, binary). Night-to-night associations between LEDS and absolute differences in nightly sleep onset timing were also evaluated with distributed lag non-linear models and mixed models.ResultsIn between-individual linear and logistic models adjusted for demographic, health, and seasonal factors, every 5-lux unit increase in LEDS was associated with an increase of 7.8 minutes in sleep onset SD (β=0.13 hours, 95%CI:0.09-0.17) and 40% greater odds (OR=1.40, 95%CI:1.24-1.60) of irregular sleep onset. In within-individual night-to-night mixed model analyses, every 5-lux unit increase in LEDS the night prior (lag0) was associated with a 2.2-minute greater deviation of sleep onset the next night (β=0.036 hours, p<0.05). Conversely, every 1-hour increase in sleep deviation (lag0) was associated with a 0.35-lux increase in future LEDS (β=0.347 lux, p<0.05).ConclusionLEDS was associated with greater irregularity in sleep onset in between-individual analyses and subsequent deviation in sleep timing in within-individual analyses, supporting a role for LEDS in exacerbating irregular sleep onset timing. Greater deviation in sleep onset was also associated with greater future LEDS, suggesting a bidirectional relationship. Maintaining a dark sleeping environment and preventing LEDS may promote sleep regularity and following a regular sleep schedule may limit LEDS.

Dataset Information

Tobacco exposure-related alterations in DNA methylation and gene expression in human monocytes: the Multi-Ethnic Study of Atherosclerosis (MESA).

Publications

Tobacco exposure-related alterations in DNA methylation and gene expression in human monocytes: the Multi-Ethnic Study of Atherosclerosis (MESA).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets