Long-term exposure to ambient fine particulate components and leukocyte epigenome-wide DNA Methylation in older men: the Normative Aging Study

Environmental Health

Research

Zongli Xu¹  Brent A. Coull²  Andrea A. Baccarelli³  Adjani A. Peralta⁴  Cuicui Wang⁴  Yaguang Wei⁴  Xinye Qiu⁴  Anna Kosheleva⁴  Joel D. Schwartz⁵  Heresh Amini⁶  Mahdieh Danesh Yazdi⁷  Jonathan Heiss⁸  Allan Just⁸  Yinan Zheng⁹  Lifang Hou⁹ 

[1]Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, Durham, NC, USA

[2]Department of Biostatistics, Harvard T. H. Chan School of Public Health, 02115, Boston, MA, USA

[3]Department of Environmental Health Sciences, Columbia Mailman School of Public Health, 10032, New York, NY, USA

[4]Department of Environmental Health, Harvard T.H. Chan School of Public Health, 02115, Boston, MA, USA

[5]Department of Environmental Health, Harvard T.H. Chan School of Public Health, 02115, Boston, MA, USA

[6]Department of Epidemiology, Harvard T.H. Chan School of Public Health, 02115, Boston, MA, USA

[7]Department of Environmental Health, Harvard T.H. Chan School of Public Health, 02115, Boston, MA, USA

[8]Department of Public Health, Faculty of Health and Medical Sciences, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark

[9]Department of Environmental Health, Harvard T.H. Chan School of Public Health, 02115, Boston, MA, USA

[10]Program in Public Health, Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA

[11]Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA

[12]Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL, USA

关键词: PM components;    Sources;    DNA methylation;    Epigenome-wide association study;    Pathway analyses;   

DOI  :  10.1186/s12940-023-01007-5

 received in 2023-02-08, accepted in 2023-07-26,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundEpigenome-wide association studies of ambient fine particulate matter (PM2.5) have been reported. However, few have examined PM2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources.MethodsWe predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000–2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways.ResultsWe included 669 men with 1,178 visits between 2000–2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic.ConclusionsOur findings showed that the effects of PM2.5 on DNAm varied by its PMCs and sources.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

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