Epigenetics of single-site and multi-site atherosclerosis in African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA).
Epigenetics of single-site and multi-site atherosclerosis in African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA).
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DOI：
10.1186/s13148-022-01229-3
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发表时间：
2022-01-17
影响因子：
5.7
通讯作者：
Smith JA
中科院分区：
文献类型：
--
作者：
Ammous F;Zhao W;Lin L;Ratliff SM;Mosley TH;Bielak LF;Zhou X;Peyser PA;Kardia SLR;Smith JA
DNA甲基化是一种受生活方式和环境因素调节的表观遗传机制，可能是心血管疾病（CVD）和亚临床动脉粥样硬化等复杂疾病的重要生物标志物。我们对来自动脉病遗传流行病学网络 (GENOA) 的 391 名非裔美国人的外周血样本中的 DNA 甲基化进行了基线评估，并在 5 年后和 12 年后评估了动脉粥样硬化。使用线性混合模型，我们检查了先前确定的冠状动脉钙化（CAC）和颈动脉斑块的 CpG 之间的关联，无论是单独的还是汇总为甲基化风险评分（MRSCAC 和 MRScarotid），以及动脉粥样硬化的四种测量指标（CAC、腹主动脉钙化（AAC）、踝肱指数（ABI）和基于单部位性别特异性四分位数的多部位动脉粥样硬化）措施）。我们还研究了四种表观遗传年龄加速测量（IEAA、EEAA、PhenoAge 加速和 GrimAge 加速）与四种动脉粥样硬化测量之间的关联。最后，我们使用基线后 5 年重复测量的 DNA 甲基化来表征表观遗传测量的时间稳定性 (N = 193)。调整CVD危险因素后，四种CpG（cg05575921（AHRR）、cg09935388（GFI1）、cg21161138（AHRR）和cg18168448（LRRC52））与多部位动脉粥样硬化相关（FDR < 0.1）。 cg05575921 也与 AAC 相关，cg09935388 与 ABI 相关。 MRSCAC 与 ABI 相关（Beta = 0.016，P = 0.006），MRScarotid 与 AAC（Beta = 0.605，相当于 AAC Agatston 评分增加约 1.8 倍，P = 0.004）和多部位动脉粥样硬化相关（β = 0.691，P = 0.002）。 GrimAge 加速度增加 5 年 (~ 1 SD) 与 AAC Agatston 评分增加 1.6 倍 (P = 0.012) 和多部位动脉粥样硬化增加 0.7 单位 (P = 0.0003) 相关，所有这些都是在调整 CVD 危险因素后。所有表观遗传测量在 5 年内都相对稳定，观察到 MRScarotid 和 GrimAge 加速的组内相关系数最高（分别为 0.87 和 0.89）。我们在非裔美国人样本中的多个血管部位发现了 DNA 甲基化与动脉粥样硬化之间存在关联的证据。有必要对这些潜在的生物标志物进行进一步评估，以加深我们对表观遗传学与动脉粥样硬化之间关系的理解。在线版本包含可在 10.1186/s13148-022-01229-3 获取的补充材料。
DNA methylation, an epigenetic mechanism modulated by lifestyle and environmental factors, may be an important biomarker of complex diseases including cardiovascular diseases (CVD) and subclinical atherosclerosis. DNA methylation in peripheral blood samples from 391 African-Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) was assessed at baseline, and atherosclerosis was assessed 5 and 12 years later. Using linear mixed models, we examined the association between previously identified CpGs for coronary artery calcification (CAC) and carotid plaque, both individually and aggregated into methylation risk scores (MRSCAC and MRScarotid), and four measures of atherosclerosis (CAC, abdominal aorta calcification (AAC), ankle–brachial index (ABI), and multi-site atherosclerosis based on gender-specific quartiles of the single-site measures). We also examined the association between four epigenetic age acceleration measures (IEAA, EEAA, PhenoAge acceleration, and GrimAge acceleration) and the four atherosclerosis measures. Finally, we characterized the temporal stability of the epigenetic measures using repeated DNA methylation measured 5 years after baseline (N = 193). After adjusting for CVD risk factors, four CpGs (cg05575921(AHRR), cg09935388 (GFI1), cg21161138 (AHRR), and cg18168448 (LRRC52)) were associated with multi-site atherosclerosis (FDR < 0.1). cg05575921 was also associated with AAC and cg09935388 with ABI. MRSCAC was associated with ABI (Beta = 0.016, P = 0.006), and MRScarotid was associated with both AAC (Beta = 0.605, equivalent to approximately 1.8-fold increase in the Agatston score of AAC, P = 0.004) and multi-site atherosclerosis (Beta = 0.691, P = 0.002). A 5-year increase in GrimAge acceleration (~ 1 SD) was associated with a 1.6-fold (P = 0.012) increase in the Agatston score of AAC and 0.7 units (P = 0.0003) increase in multi-site atherosclerosis, all after adjusting for CVD risk factors. All epigenetic measures were relatively stable over 5 years, with the highest intraclass correlation coefficients observed for MRScarotid and GrimAge acceleration (0.87 and 0.89, respectively). We found evidence of an association between DNA methylation and atherosclerosis at multiple vascular sites in a sample of African-Americans. Further evaluation of these potential biomarkers is warranted to deepen our understanding of the relationship between epigenetics and atherosclerosis. The online version contains supplementary material available at 10.1186/s13148-022-01229-3.
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全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
3.5
作者：
Besingi, Welisane;Johansson, Asa
通讯作者：
Johansson, Asa
影响因子：
--
作者：
Fortin, Jean-Philippe;Fertig, Elana;Hansen, Kasper
通讯作者：
Hansen, Kasper
DOI：
10.1016/0735-1097(90)90282-t
发表时间：
1990-03-15
影响因子：
24
作者：
AGATSTON, AS;JANOWITZ, WR;DETRANO, R
通讯作者：
DETRANO, R
影响因子：
158.5
作者：
CRIQUI, MH;LANGER, RD;BROWNER, D
通讯作者：
BROWNER, D