Residential surrounding greenness and DNA methylation: An epigenome-wide association study

Rongbin Xu; Shuai Li; Shanshan Li; Ee Ming Wong; Melissa C Southey; John L Hopper; Michael J Abramson; Yuming Guo

doi:10.1016/j.envint.2021.106556

Residential surrounding greenness and DNA methylation: An epigenome-wide association study

Environ Int. 2021 Sep:154:106556. doi: 10.1016/j.envint.2021.106556. Epub 2021 Apr 13.

Authors

Rongbin Xu¹, Shuai Li², Shanshan Li¹, Ee Ming Wong³, Melissa C Southey⁴, John L Hopper⁵, Michael J Abramson¹, Yuming Guo⁶

Affiliations

¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia.
² Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3800, Australia.
³ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3800, Australia; Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC 3010, Australia.
⁴ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3800, Australia; Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC 3010, Australia; Cancer Epidemiology Division, Cancer Council Victoria, VIC 3004, Australia.
⁵ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia.
⁶ School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia. Electronic address: yuming.guo@monash.edu.

PMID: 33862401
DOI: 10.1016/j.envint.2021.106556

Abstract

Background: DNA methylation is a potential biological mechanism through which residential greenness affects health, but little is known about its association with greenness and whether the association could be modified by genetic background. We aimed to evaluate the association between surrounding greenness and genome-wide DNA methylation and potential gene-greenness interaction effects on DNA methylation.

Methods: We measured blood-derived DNA methylation using the HumanMethylation450 BeadChip array (Illumina) for 479 Australian women, including 66 monozygotic, 66 dizygotic twin pairs, and 215 sisters of these twins. Surrounding greenness was represented by Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) within 300, 500, 1000 or 2000 m surrounding participants' home addresses. For each cytosine-guanine dinucleotide (CpG), the associations between its methylation level and NDVI or EVI were evaluated by generalized estimating equations, after adjusting for age, education, marital status, area-level socioeconomic status, smoking behavior, cell-type proportions, and familial clustering. We used comb-p and DMRcate to identify significant differentially methylated regions (DMRs). For each significant CpG, we evaluated the interaction effects of greenness and single-nucleotide polymorphisms (SNPs) within ±1 Mb window on its methylation level.

Results: We found associations between surrounding greenness and blood DNA methylation for one CpG (cg04720477, mapped to the promoter region of CNP gene) with false discovery rate [FDR] < 0.05, and for another 9 CpGs with 0.05 ≤ FDR < 0.10. For two of these CpGs, we found 33 SNPs significantly (FDR < 0.05) modified the greenness-methylation association. There were 35 significant DMRs related to surrounding greenness that were identified by both comb-p (Sidak p-value < 0.01) and DMRcate (FDR < 0.01). Those CpGs and DMRs were mapped to genes related to many human diseases, such as mental health disorders and neoplasms as well as nutritional and metabolic diseases.

Conclusions: Surrounding greenness was associated with blood DNA methylation of many loci across human genome, and this association could be modified by genetic variations.

Keywords: DNA methylation; Epigenetics; Epigenome-wide association study; Gene-environment interaction; Greenness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Australia
DNA Methylation*
Epigenesis, Genetic
Epigenome*
Female
Genome-Wide Association Study
High-Throughput Nucleotide Sequencing
Humans
Smoking