住宅周边绿化与 DNA 甲基化：一项全基因组关联研究。
Residential surrounding greenness and DNA methylation: An epigenome-wide association study.
机构信息
School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia.
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.
出版信息
Environ Int. 2021 Sep;154:106556. doi: 10.1016/j.envint.2021.106556. Epub 2021 Apr 13.
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.
背景
DNA 甲基化是住宅绿化影响健康的一种潜在生物学机制，但人们对其与绿化的关联以及这种关联是否可以通过遗传背景来修饰知之甚少。我们旨在评估周围绿化与全基因组 DNA 甲基化之间的关联，以及绿化与 DNA 甲基化之间潜在的基因-绿化相互作用效应。
方法
我们使用 Illumina 公司的 HumanMethylation450 BeadChip 芯片（Illumina）测量了 479 名澳大利亚女性的血液衍生 DNA 甲基化水平，其中包括 66 对同卵双胞胎、66 对异卵双胞胎和 215 对双胞胎的姐妹。周围绿化用归一化植被指数（NDVI）和增强型植被指数（EVI）来表示，范围在参与者家庭住址周围 300、500、1000 或 2000 米以内。对于每个胞嘧啶-鸟嘌呤二核苷酸（CpG），在调整年龄、教育程度、婚姻状况、地区社会经济地位、吸烟行为、细胞类型比例和家族聚类后，通过广义估计方程评估其甲基化水平与 NDVI 或 EVI 之间的关联。我们使用 comb-p 和 DMRcate 来识别显著的差异甲基化区域（DMRs）。对于每个显著的 CpG，我们评估了绿色与 ±1 Mb 窗口内的单核苷酸多态性（SNP）对其甲基化水平的相互作用效应。
结果
我们发现，一个 CpG（cg04720477，映射到 CNP 基因的启动子区域）的周围绿化与血液 DNA 甲基化之间存在关联，假发现率 [FDR] < 0.05，另有 9 个 CpG 的 FDR < 0.10。对于这两个 CpG，我们发现有 33 个 SNP 显著（FDR < 0.05）修饰了绿色与甲基化的关联。通过 comb-p（Sidak p 值 < 0.01）和 DMRcate（FDR < 0.01）都鉴定出了与周围绿化相关的 35 个显著的 DMR。这些 CpG 和 DMR 映射到与许多人类疾病相关的基因上，如精神健康障碍和肿瘤以及营养和代谢疾病。
结论
周围绿化与人类基因组中许多基因座的血液 DNA 甲基化有关，这种关联可以通过遗传变异来修饰。
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