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- Title
Epigenome- wide analysis of DNA methylation and coronary heart disease: a nested case- control study.
- Authors
Jiahui Si; Songchun Yang; Dianjianyi Sun; Canqing Yu; Yu Guo; Yifen Lin; Millwood, Iona Y.; Walters, Robin G.; Ling Yang; Yiping Chen; Huaidong Du; Yujie Hua; Jingchao Liu; Junshi Chen; Zhengming Chen; Wei Chen; Jun Lv; Liming Liang; Liming Li
- Abstract
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.
- Subjects
EPIGENOMICS; DNA methylation; CORONARY disease; DNA analysis; DIASTOLIC blood pressure; SYSTOLIC blood pressure
- Publication
eLife, 2021, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.68671