Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study
Background: Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:08f7c4351bf949d8ae138b5d153758552021-11-17T14:23:27ZEpigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study10.7554/eLife.686712050-084Xe68671https://doaj.org/article/08f7c4351bf949d8ae138b5d153758552021-09-01T00:00:00Zhttps://elifesciences.org/articles/68671https://doaj.org/toc/2050-084XBackground: Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population. Methods: We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10 year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module. Results: After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR < 0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47 % decrease to a 118 % increase. Mediation analyses revealed 28.5 % of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of ANKS1A gene (P for mediation effect = 0.036). Methylation level at the promoter region of SNX30 was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7 % (P = 0.003) via systolic blood pressure and 6.4 % (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD. Conclusions: We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and blood pressure-related pathways to CHD risk. Funding: This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01).Jiahui SiSongchun YangDianjianyi SunCanqing YuYu GuoYifei LinIona Y MillwoodRobin G WaltersLing YangYiping ChenHuaidong DuYujie HuaJingchao LiuJunshi ChenZhengming ChenWei ChenJun LvLiming LiangLiming LiChina Kadoorie Biobank Collaborative GroupeLife Sciences Publications Ltdarticlecoronary heart diseaseepigeneticsDNA methylationepidemiologyMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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DOAJ |
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EN |
| topic |
coronary heart disease epigenetics DNA methylation epidemiology Medicine R Science Q Biology (General) QH301-705.5 |
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coronary heart disease epigenetics DNA methylation epidemiology Medicine R Science Q Biology (General) QH301-705.5 Jiahui Si Songchun Yang Dianjianyi Sun Canqing Yu Yu Guo Yifei Lin Iona Y Millwood Robin G Walters Ling Yang Yiping Chen Huaidong Du Yujie Hua Jingchao Liu Junshi Chen Zhengming Chen Wei Chen Jun Lv Liming Liang Liming Li China Kadoorie Biobank Collaborative Group Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
| description |
Background: Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population.
Methods: We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10 year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module.
Results: After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR < 0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47 % decrease to a 118 % increase. Mediation analyses revealed 28.5 % of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of ANKS1A gene (P for mediation effect = 0.036). Methylation level at the promoter region of SNX30 was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7 % (P = 0.003) via systolic blood pressure and 6.4 % (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD.
Conclusions: We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and blood pressure-related pathways to CHD risk.
Funding: This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01). |
| format |
article |
| author |
Jiahui Si Songchun Yang Dianjianyi Sun Canqing Yu Yu Guo Yifei Lin Iona Y Millwood Robin G Walters Ling Yang Yiping Chen Huaidong Du Yujie Hua Jingchao Liu Junshi Chen Zhengming Chen Wei Chen Jun Lv Liming Liang Liming Li China Kadoorie Biobank Collaborative Group |
| author_facet |
Jiahui Si Songchun Yang Dianjianyi Sun Canqing Yu Yu Guo Yifei Lin Iona Y Millwood Robin G Walters Ling Yang Yiping Chen Huaidong Du Yujie Hua Jingchao Liu Junshi Chen Zhengming Chen Wei Chen Jun Lv Liming Liang Liming Li China Kadoorie Biobank Collaborative Group |
| author_sort |
Jiahui Si |
| title |
Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
| title_short |
Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
| title_full |
Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
| title_fullStr |
Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
| title_full_unstemmed |
Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
| title_sort |
epigenome-wide analysis of dna methylation and coronary heart disease: a nested case-control study |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/08f7c4351bf949d8ae138b5d15375855 |
| work_keys_str_mv |
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| _version_ |
1718425395135512576 |