探讨吸烟行为、血液 DNA 甲基化谱与冠心病和心肌梗死发展之间的潜在因果关系。
Examining the potential causal relationships among smoking behaviors, blood DNA methylation profiles, and the development of coronary heart disease and myocardial infarction.
机构信息
Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
出版信息
Clin Epigenetics. 2024 Nov 29;16(1):173. doi: 10.1186/s13148-024-01791-y.
BACKGROUND
Smoking has been identified as a standalone risk factor for coronary heart disease (CHD) and myocardial infarction (MI), but the precise underlying mechanisms remain incompletely elucidated.
RESULTS
In this study, we conducted a two-sample Mendelian randomization analysis to examine the impact of smoking behaviors (including smoking initiation, age of smoking initiation, cigarettes per day, and smoking cessation) and smoking-related DNA methylation at CpG sites on CHD and MI based on the UK Biobank dataset. Additionally, we included the FinnGen and Biobank Japan datasets as replications and performed a meta-analysis to combine the results from different data sources. We further validated our results using genetic colocalization analysis. In genomic analysis, we provided compelling evidence on the association between genetically predicted smoking initiation and increased susceptibility to CHD and MI. In epigenetic analysis, we identified 11 smoking-related CpG sites linked to CHD risk and 10 smoking-related CpG sites associated with the risk of MI based on the UK Biobank dataset. Subsequently, some of these CpG sites were further replicated using the FinnGen or BBJ datasets. Ultimately, a meta-analysis was conducted to integrate findings from various data sources (3 for CHD, and 2 for MI), revealing that 7 of 11 CpG sites were linked to CHD risk; whereas, 7 of 10 CpG sites were associated with MI risk. Furthermore, we performed genetic colocalization analysis and found that cg19744173 (FBLN7), cg00395063 (ARHGEF12), and cg16822035 (MCF2L) exhibited robust evidence of colocalization with coronary heart disease; whereas, cg19529732 (DIABLO), cg26405020 (FES), and cg08940075 (CNN3) demonstrated strong colocalization evidence with the risk of myocardial infarction.
CONCLUSIONS
Our research offers a novel insight into the impact of smoking on the susceptibility to CHD and MI through the lens of epigenetic DNA methylation.
背景
吸烟已被确定为冠心病（CHD）和心肌梗死（MI）的独立危险因素，但确切的潜在机制仍不完全清楚。
结果
本研究基于英国生物库（UK Biobank）数据集，采用两样本孟德尔随机化分析方法，研究吸烟行为（包括吸烟起始年龄、吸烟起始年龄、每天吸烟量和戒烟）和与 CpG 位点相关的吸烟相关 DNA 甲基化对 CHD 和 MI 的影响。此外，我们还纳入了 FinnGen 和日本生物银行（Biobank Japan）数据集作为重复，并进行了荟萃分析，以结合不同数据源的结果。我们还使用遗传共定位分析进一步验证了我们的结果。在基因组分析中，我们提供了有力的证据表明，遗传预测的吸烟起始与 CHD 和 MI 的易感性增加有关。在表观遗传分析中，我们在 UK Biobank 数据集上确定了 11 个与 CHD 风险相关的与吸烟相关的 CpG 位点和 10 个与 MI 风险相关的与吸烟相关的 CpG 位点。随后，使用 FinnGen 或 BBJ 数据集对其中一些 CpG 位点进行了进一步的重复验证。最终，进行了荟萃分析以整合来自不同数据源（CHD 为 3 个，MI 为 2 个）的研究结果，结果表明 11 个 CpG 位点中有 7 个与 CHD 风险相关；而 10 个 CpG 位点中有 7 个与 MI 风险相关。此外，我们进行了遗传共定位分析，发现 cg19744173（FBLN7）、cg00395063（ARHGEF12）和 cg16822035（MCF2L）与冠心病有明显的共定位证据；而 cg19529732（DIABLO）、cg26405020（FES）和 cg08940075（CNN3）与心肌梗死的风险有很强的共定位证据。
结论
本研究通过 DNA 甲基化的表观遗传学视角，为吸烟对 CHD 和 MI 易感性的影响提供了新的见解。
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