Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study
<br><strong>Background:</strong> 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 met...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
eLife Sciences Publications
2021
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| _version_ | 1797110441730637824 |
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| author | Si, J Yang, S Sun, D Yu, C Guo, Y Lin, Y Millwood, I Walters, R Yang, L Chen, Y Du, H Hua, Y Liu, J Chen, J Chen, Z Chen, W Li, L Liang, L Lv, J |
| author2 | China Kadoorie Biobank Collaborative Group |
| author_facet | China Kadoorie Biobank Collaborative Group Si, J Yang, S Sun, D Yu, C Guo, Y Lin, Y Millwood, I Walters, R Yang, L Chen, Y Du, H Hua, Y Liu, J Chen, J Chen, Z Chen, W Li, L Liang, L Lv, J |
| author_sort | Si, J |
| collection | OXFORD |
| description | <br><strong>Background:</strong> 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.
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Methods:</strong> 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.
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Results: </strong>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.
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Conclusions: </strong>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 BP-related pathways to CHD risk.
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Funding:</strong> 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 and Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01). |
| first_indexed | 2024-03-07T07:54:54Z |
| format | Journal article |
| id | oxford-uuid:b0eb9583-dea8-4dbe-b9b5-58d99a1a489b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:54:54Z |
| publishDate | 2021 |
| publisher | eLife Sciences Publications |
| record_format | dspace |
| spelling | oxford-uuid:b0eb9583-dea8-4dbe-b9b5-58d99a1a489b2023-08-09T10:36:36ZEpigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b0eb9583-dea8-4dbe-b9b5-58d99a1a489bEnglishSymplectic ElementseLife Sciences Publications2021Si, JYang, SSun, DYu, CGuo, YLin, YMillwood, IWalters, RYang, LChen, YDu, HHua, YLiu, JChen, JChen, ZChen, WLi, LLiang, LLv, JChina Kadoorie Biobank Collaborative Group<br><strong>Background:</strong> 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. <br><strong> Methods:</strong> 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. <br><strong> Results: </strong>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. <br><strong> Conclusions: </strong>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 BP-related pathways to CHD risk. <br><strong> Funding:</strong> 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 and Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01). |
| spellingShingle | Si, J Yang, S Sun, D Yu, C Guo, Y Lin, Y Millwood, I Walters, R Yang, L Chen, Y Du, H Hua, Y Liu, J Chen, J Chen, Z Chen, W Li, L Liang, L Lv, J Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
| title | 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_short | 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 |
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