Wu Yao, Xu Rongbin, Li Shanshan, Ming Wong Ee, Southey Melissa C, Hopper John L, Abramson Michael J, Li Shuai, Guo Yuming
School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia.
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.
Environ Int. 2023 Jan;171:107655. doi: 10.1016/j.envint.2022.107655. Epub 2022 Nov 24.
Temperature fluctuations can affect human health independent of the effect of mean temperature. However, no study has evaluated whether short-term temperature fluctuations could affect DNA methylation.
Peripheral blood DNA methylation for 479 female siblings of 130 families were analysed. Gridded daily temperatures data were obtained, linked to each participant's home address, and used to calculate nine different metrics of short-term temperature fluctuations: temperature variabilities (TVs) within the day of blood draw and preceding one to seven days (TV 0-1 to TV 0-7), diurnal temperature range (DTR), and temperature change between neighbouring days (TCN). Within-sibship design was used to perform epigenome-wide association analyses, adjusting for daily mean temperatures, and other important covariates (e.g., smoking, alcohol use, cell-type proportions). Differentially methylated regions (DMRs) were further identified. Multiple-testing comparisons with a significant threshold of 0.01 for cytosine-guanine dinucleotides (CpGs) and 0.05 for DMRs were applied.
Among 479 participants (mean age ± SD, 56.4 ± 7.9 years), we identified significant changes in methylation levels in 14 CpGs and 70 DMRs associated with temperature fluctuations. Almost all identified CpGs were associated with exposure to temperature fluctuations within three days. Differentially methylated signals were mapped to 68 genes that were linked to human diseases such as cancer (e.g., colorectal carcinoma, breast carcinoma, and metastatic neoplasms) and mental disorder (e.g., schizophrenia, mental depression, and bipolar disorder). The top three most significantly enriched gene ontology terms were Response to bacterium (TV 0-3), followed by Hydrolase activity, acting on ester bonds (TCN), and Oxidoreductase activity (TV 0-3).
Short-term temperature fluctuations were associated with differentially methylated signals across the human genome, which provides evidence on the potential biological mechanisms underlying the health impact of temperature fluctuations. Future studies are needed to further clarify the roles of DNA methylation in diseases associated with temperature fluctuations.
温度波动可独立于平均温度的影响而对人类健康产生影响。然而，尚无研究评估短期温度波动是否会影响DNA甲基化。
分析了130个家庭中479名女性同胞的外周血DNA甲基化情况。获取网格化的每日温度数据，并将其与每位参与者的家庭住址相关联，用于计算九种不同的短期温度波动指标：采血当天及前1至7天内的温度变异性（TVs）（TV 0-1至TV 0-7）、昼夜温度范围（DTR）以及相邻两天之间的温度变化（TCN）。采用同胞配对设计进行全表观基因组关联分析，并对每日平均温度和其他重要协变量（如吸烟、饮酒、细胞类型比例）进行校正。进一步鉴定差异甲基化区域（DMRs）。对胞嘧啶-鸟嘌呤二核苷酸（CpGs）采用显著阈值为0.01、对DMRs采用显著阈值为0.05进行多重检验比较。
在479名参与者（平均年龄±标准差，56.4±7.9岁）中，我们鉴定出14个CpGs和70个DMRs的甲基化水平与温度波动存在显著变化。几乎所有鉴定出的CpGs都与三天内的温度波动暴露有关。差异甲基化信号映射到68个基因，这些基因与人类疾病如癌症（如结肠直肠癌、乳腺癌和转移性肿瘤）和精神障碍（如精神分裂症、精神抑郁和双相情感障碍）相关。最显著富集的前三个基因本体术语分别是对细菌的反应（TV 0-3）、作用于酯键的水解酶活性（TCN）和氧化还原酶活性（TV 0-3）。
短期温度波动与全人类基因组的差异甲基化信号相关，这为温度波动对健康影响的潜在生物学机制提供了证据。未来需要进一步研究以阐明DNA甲基化在与温度波动相关疾病中的作用。
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