Nature Communications (Aug 2024)
Genome-wide DNA methylation profiling in blood reveals epigenetic signature of incident acute coronary syndrome
- Pinpin Long,
- Jiahui Si,
- Ziwei Zhu,
- Yi Jiang,
- Yufei Wang,
- Qin Jiang,
- Wending Li,
- Xuedan Xu,
- Yutong You,
- Minghan Qu,
- Huihui Wang,
- Tingting Mo,
- Kang Liu,
- Jing Jiang,
- Qiuhong Wang,
- Canqing Yu,
- Yu Guo,
- Iona Y. Millwood,
- Robin G. Walters,
- Ximiao He,
- Yu Yuan,
- Hao Wang,
- Xiaomin Zhang,
- Meian He,
- Huan Guo,
- Zhengming Chen,
- Liming Li,
- Jun Lv,
- Chaolong Wang,
- Tangchun Wu
Affiliations
- Pinpin Long
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Jiahui Si
- National Institute of Health Data Science at Peking University, Peking University
- Ziwei Zhu
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Yi Jiang
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Yufei Wang
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Qin Jiang
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Wending Li
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Xuedan Xu
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Yutong You
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Minghan Qu
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Huihui Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Tingting Mo
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Kang Liu
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Jing Jiang
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Qiuhong Wang
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Canqing Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center
- Yu Guo
- Fuwai Hospital, Chinese Academy of Medical Sciences
- Iona Y. Millwood
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford
- Robin G. Walters
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford
- Ximiao He
- Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology
- Yu Yuan
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Hao Wang
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Xiaomin Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Meian He
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Huan Guo
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Zhengming Chen
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford
- Liming Li
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center
- Jun Lv
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center
- Chaolong Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- Tangchun Wu
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
- DOI
- https://doi.org/10.1038/s41467-024-51751-6
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 11
Abstract
Abstract DNA methylation (DNAm) has been implicated in acute coronary syndrome (ACS), but the causality remains unclear in cross-sectional studies. Here, we conduct a prospective epigenome-wide association study of incident ACS in two Chinese cohorts (discovery: 751 nested case-control pairs; replication: 476 nested case-control pairs). We identified and validated 26 differentially methylated positions (DMPs, false discovery rate [FDR] <0.05), including three mapped to known cardiovascular disease genes (PRKCZ, PRDM16, EHBP1L1) and four with causal evidence from Mendelian randomization (PRKCZ, TRIM27, EMC2, EHBP1L1). Two hypomethylated DMPs were negatively correlated with the expression in blood of their mapped genes (PIGG and EHBP1L1), which were further found to overexpress in leukocytes and/or atheroma plaques. Finally, our DMPs could substantially improve the prediction of ACS over traditional risk factors and polygenic scores. These findings demonstrate the importance of DNAm in the pathogenesis of ACS and highlight DNAm as potential predictive biomarkers and treatment targets.
