Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation

Abstract

Background: DNA methylation (DNAm) may contribute to processes that underlie associations between air pollution and poor health. Therefore, our objective was to evaluate associations between DNAm and ambient concentrations of particulate matter (PM) ≤2.5, ≤10, and 2.5–10 μm in diameter (PM 2.5 ; PM 10 ; PM 2.5–10 ). Methods: We conducted a methylome-wide association study among twelve cohort- and race/ethnicity-stratified subpopulations from the Women’s Health Initiative and the Atherosclerosis Risk in Communities study ( n = 8397; mean age: 61.5 years; 83% female; 45% African American; 9% Hispanic/Latino American). We averaged geocoded address-specific estimates of daily and monthly mean PM concentrations over 2, 7, 28, and 365 days and 1 and 12 months before exams at which we measured leukocyte DNAm in whole blood. We estimated subpopulation-specific, DNAm-PM associations at approximately 485,000 Cytosine-phosphate-Guanine (CpG) sites in multi-level, linear, mixed-effects models. We combined subpopulation- and site-specific estimates in fixed-effects, inverse variance-weighted meta-analyses, then for associations that exceeded methylome-wide significance and were not heterogeneous across subpopulations ( P < 1.0 × 10 −7 ; P Cochran’s Q > 0.10), we characterized associations using publicly accessible genomic databases and attempted replication in the Cooperative Health Research in the Region of Augsburg (KORA) study. Results: Analyses identified significant DNAm-PM associations at three CpG sites. Twenty-eight-day mean PM 10 was positively associated with DNAm at cg19004594 (chromosome 20; MATN4 ; P = 3.33 × 10 −8 ). One-month mean PM 10 and PM 2.5–10 were positively associated with DNAm at cg24102420 (chromosome 10; ARPP21 ; P = 5.84 × 10 −8 ) and inversely associated with DNAm at cg12124767 (chromosome 7; CFTR ; P = 9.86 × 10 −8 ). The PM-sensitive CpG sites mapped to neurological, pulmonary, endocrine, and cardiovascular disease-related genes, but DNAm at those sites was not associated with gene expression in blood cells and did not replicate in KORA. Conclusions: Ambient PM concentrations were associated with DNAm at genomic regions potentially related to poor health among racially, ethnically and environmentally diverse populations of U.S. women and men. Further investigation is warranted to uncover mechanisms through which PM-induced epigenomic changes may cause disease.

Use of an Exposome Approach to Understand the Effects of Exposures From the Natural, Built, and Social Environments on Cardio-Vascular Disease Onset, Progression, and Outcomes

“…DNA methylation also provides the potential for a biomarker of exposure to reflect environmental and lifestyle risk factors and a biomarker of effect to demonstrate susceptibility to exposureassociated diseases. Although DNA methylation is structurally stable by a covalent modification (123), it can be modified by environmental exposure that leads to disease, including CVD or increased risk for developing CVD (120)(121)(122)(125)(126)(127)(128)(129)(130)(131)(132)(133)(134)(135)(136).…”

Genome-Wide DNA Methylation in Peripheral Blood and Long-Term Exposure to Source-Specific Transportation Noise and Air Pollution: The SAPALDIA Study

“…DNA methylation alterations may mediate part of the physiological and biochemical changes leading from these traffic-related exposures to their associated preclinical and clinical phenotypes. Increasing evidence has linked short-and long-term air pollution exposure to various measures of DNA methylation in both children and adults (Abraham et al 2018;de FC Lichtenfels et al 2018;Gondalia et al 2019;Gruzieva et al 2017;Lee et al 2019;Mostafavi et al 2018;Panni et al 2016;Plusquin et al 2017Plusquin et al , 2018Sayols-Baixeras et al 2019). Although findings from these studies were largely inconsistent with regard to single Cytosine-phosphate-Guanine (CpG) sites, the systematic review by Alfano et al (Alfano et al 2018) highlighted that air pollution was consistently linked to global hypomethylation in children (Breton et al 2016;Cai et al 2017;Janssen et al 2015) and in adults (De Nys et al 2018;De Prins et al 2013) and accelerated epigenetic aging in adults (Nwanaji-Enwerem et al 2016Ward-Caviness et al 2016).…”

“…Second, oxidative DNA damage, a correlate of altered DNA methylation and gene expression (Russo et al 2016) was linked to occupational noise (Bagheri Hosseinabadi et al 2019;Nawaz and Hasnain 2013) and traffic noise (Hemmingsen et al 2015). Third, DNA methylation changes were reported for noise-related stressors such as vehicular traffic (Commodore et al 2018) and insufficient sleep (Gaine et al 2018). Methylation changes were also reported in circadian rhythm genes in conditions of acute sleep loss (Cedernaes et al 2015) and night-shift work (Zhu et al 2011).…”

Epigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention

“…DNA methylation has been shown to be associated with various other environmental exposures, including aging [41,42], BMI [43][44][45][46][47][48][49], physical activity and inactivity [50,51], air pollution [52][53][54], stress [55,56], depression [57], and alcohol [58][59][60][61] (Table 1). Remarkably, methylation of CDC42BPB (cg04987734) was shown to be able to classify individuals with respect to heavy alcohol consumption from non-drinkers with an AUC of 0.88.…”