Epigenome-wide analysis of long-term air pollution exposure and DNA methylation in monocytes: results from the Multi-Ethnic Study of Atherosclerosis
Creators: name: Chi, Gloria C.
name: Liu, Yongmei
name: MacDonald, James W.
name: Reynolds, Lindsay M.
name: Enquobahrie, Daniel A.
name: Fitzpatrick, Annette L.
name: Kerr, Kathleen F.
name: Budoff, Matthew J.
name: Lee, Su-in
name: Siscovick, David
name: Kaufman, Joel D.
Publisher: name: Taylor & Francis
Year: 2021
Subjects: subject: Biophysics
subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Cancer
subject: Inorganic Chemistry
subject: Science Policy
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: Plant Biology

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 <i>cis</i>-gene expression. Using spatiotemporal models, one-year average concentrations of outdoor fine particulate matter (PM<sub>2.5</sub>) and oxides of nitrogen (NO<sub>X</sub>) 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 <i>cis</i>-gene expression. Four differentially methylated regions (DMRs) located on chromosomes 5, 6, 7, and 16 (within or near <i>SDHAP3, ZFP57, HOXA5</i>, and <i>PRM1</i>, respectively) were associated with PM<sub>2.5</sub>. The DMRs on chromosomes 5 and 6 also associated with NO<sub>X</sub>. The DMR on chromosome 5 had the smallest p-value for both PM<sub>2.5</sub> (p = 1.4×10<sup>−6</sup>) and NO<sub>X</sub> (p = 7.7×10<sup>−6</sup>). Three differentially methylated CpGs were identified for PM<sub>2.5</sub>, and cg05926640 (near <i>TOMM20</i>) had the smallest p-value (p = 5.6×10<sup>−8</sup>). NO<sub>X</sub> significantly associated with cg11756214 within <i>ZNF347</i> (p = 5.6×10<sup>−8</sup>). Several differentially methylated signals were also associated with <i>cis</i>-gene expression. The DMR located on chromosome 7 was associated with the expression of <i>HOXA5, HOXA9</i>, and <i>HOXA10</i>. The DMRs located on chromosomes 5 and 16 were associated with expression of <i>MRPL36</i> and <i>DEXI</i>, respectively. The CpG cg05926640 was associated with expression of <i>ARID4B, IRF2BP2</i>, and <i>TOMM20</i>. 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.