TY - JOUR
T1 - Epigenome-wide association study of short-term temperature fluctuations based on within-sibship analyses in Australian females
AU - Wu, Yao
AU - Xu, Rongbin
AU - Li, Shanshan
AU - Ming Wong, Ee
AU - Southey, Melissa C.
AU - Hopper, John L.
AU - Abramson, Michael J.
AU - Li, Shuai
AU - Guo, Yuming
N1 - Funding Information:
YW and RX are supported by China Scholarship Council (202006010044 and 201806010405). SSL is supported by an Emerging Leader Fellowship of the Australian National Health and Medical Research Council (NHMRC; GNT2009866). SL is supported by an Early Career Research Fellowship of the Victorian Cancer Agency (ECRF 19020). YG is supported by NHMRC Career Development Fellowship (GNT1163693) and Leader Fellowship (GNT2008813). MCS is supported by a NHMRC Senior Research Fellowship (APP1155163). JLH is supported by a NHMRC Senior Principal Research Fellowship. The Australian Mammographic Density Twins and Sisters Study (AMDTSS) was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (1079102 and 1050561) from the NHMRC and the Cancer Australia and National Breast Cancer Foundation (509307). The funding bodies did not play any role in the study design, data collection, data analyses, results interpretation, and writing of this manuscript.
Funding Information:
Michael Abramson holds investigator-initiated grants from Pfizer and Boehringer-Ingelheim for unrelated research. He has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi. He also received a speaker’s fee from GSK. The other authors declare no competing interests.
Funding Information:
YW and RX are supported by China Scholarship Council (202006010044 and 201806010405). SSL is supported by an Emerging Leader Fellowship of the Australian National Health and Medical Research Council (NHMRC; GNT2009866). SL is supported by an Early Career Research Fellowship of the Victorian Cancer Agency (ECRF 19020). YG is supported by NHMRC Career Development Fellowship (GNT1163693) and Leader Fellowship (GNT2008813). MCS is supported by a NHMRC Senior Research Fellowship (APP1155163). JLH is supported by a NHMRC Senior Principal Research Fellowship. The Australian Mammographic Density Twins and Sisters Study (AMDTSS) was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (1079102 and 1050561) from the NHMRC and the Cancer Australia and National Breast Cancer Foundation (509307). The funding bodies did not play any role in the study design, data collection, data analyses, results interpretation, and writing of this manuscript. The raw and processed DNA methylation data set are open accessed or free on Gene Expression Omnibus (accession number GSE100227). As required by the ethics approval, the other data (e.g. data on covariates) are not allowed to be open for access. The data could be accessed on reasonable request to J.L.H. ([email protected]). The AMDTSS was approved by the Human Research Ethics Committee of The University of Melbourne. Written informed consent was obtained from all participants. The present study was approved by the Monash University Human Research Ethics Committee. Michael Abramson holds investigator-initiated grants from Pfizer and Boehringer-Ingelheim for unrelated research. He has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi. He also received a speaker's fee from GSK. The other authors declare no competing interests.
Publisher Copyright:
© 2022 The Author(s)
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - Diurnal temperature range
KW - DNA methylation
KW - Temperature change between neighbouring days
KW - Temperature variability
KW - Twin and family study
UR - http://www.scopus.com/inward/record.url?scp=85143758959&partnerID=8YFLogxK
U2 - 10.1016/j.envint.2022.107655
DO - 10.1016/j.envint.2022.107655
M3 - Article
C2 - 36476687
AN - SCOPUS:85143758959
SN - 0160-4120
VL - 171
JO - Environment International
JF - Environment International
M1 - 107655
ER -
