Epigenome-wide association study of short-term temperature fluctuations based on within-sibship analyses in Australian females

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

doi:10.1016/j.envint.2022.107655

Epigenome-wide association study of short-term temperature fluctuations based on within-sibship analyses in Australian females

Environ Int. 2023 Jan:171:107655. doi: 10.1016/j.envint.2022.107655. Epub 2022 Nov 24.

Authors

Yao Wu¹, Rongbin Xu¹, Shanshan Li¹, Ee Ming Wong², Melissa C Southey³, John L Hopper⁴, Michael J Abramson¹, Shuai Li⁵, Yuming Guo⁶

Affiliations

¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia.
² 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.
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; Cancer Epidemiology Division, Cancer Council Victoria, VIC 3004, Australia.
⁴ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia.
⁵ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3800, 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; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia.
⁶ School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia. Electronic address: yuming.guo@monash.edu.

PMID: 36476687
DOI: 10.1016/j.envint.2022.107655

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: DNA methylation; Diurnal temperature range; Temperature change between neighbouring days; Temperature variability; Twin and family study.

Publication types

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

MeSH terms

Australia
DNA Methylation*
Epigenesis, Genetic
Epigenome*
Female
Genome-Wide Association Study
Humans
Smoking
Temperature