A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events.
A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events.
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DOI：
10.1186/s13148-022-01341-4
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发表时间：
2022-09-29
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
最近的证据强调了血液DNA甲基化（DNAm）作为非传染性疾病（NCD）风险因素暴露的替代生物标志物的流行病学价值。在许多情况下，DNAm替代暴露比自我报告或测量暴露更能预测疾病和寿命。因此，基于血液dna替代物的疾病预测模型可能优于目前最先进的预测模型。本研究旨在开发新的DNAm替代物用于心血管疾病（CVD）危险因素，并开发一种预测CVD风险的复合生物标志物。我们将新开发的风险评分与最先进的心血管疾病DNAm风险评分、“下一代”表观遗传时钟DNAmGrimAge和基于传统风险因素SCORE2的预测模型进行了比较。利用EPIC意大利队列的数据，我们获得了新的DNAm替代品，用于BMI、血压、空腹血糖和胰岛素、胆固醇、甘油三酯和凝血生物标志物。我们在来自欧洲和美国的四个独立数据集中验证了它们。此外，我们推导了dnamcvd评分作为几个DNAm替代指标的组合来预测到cvd事件的时间。ROC曲线分析显示，dnamcvd评分优于先前开发的CVD风险评分和短期CVD风险评分SCORE2。有趣的是，DNAmGrimAge和DNAmCVDscore的性能是相当的（DNAmGrimAge稍微低一些，尽管差异没有统计学意义）。我们描述了对未来分子流行病学研究有用的CVD危险因素的新型DNAm替代品，我们描述了基于血液DNAm的复合生物标志物dnamcvd评分，预测短期心血管事件。我们的研究结果强调了DNAm替代生物标志物在表观遗传流行病学中识别高危人群的有用性。此外，我们还提供了基于DNAm替代物的预测模型有效性的进一步证据，并讨论了进一步改进的方法方面。最后，我们的研究结果鼓励通过培训和开发针对疾病特定风险因素和暴露的dna替代品，在其他非传染性疾病中测试这种方法。在线版本包含补充材料，可在10.1186/s13148-022-01341-4获得。
Recent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predicts diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-the-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-the-art DNAm risk scores for cardiovascular diseases, the ‘next-generation’ epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2. Using data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent data sets from Europe and the USA. Further, we derived a DNAmCVDscore predictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show that DNAmCVDscore outperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge and DNAmCVDscore was comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant). We described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker, DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of prediction models based on DNAm surrogates and discuss methodological aspects for further improvements. Finally, our results encourage testing this approach for other NCD diseases by training and developing DNAm surrogates for disease-specific risk factors and exposures. The online version contains supplementary material available at 10.1186/s13148-022-01341-4.
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影响因子：
7.7
作者：
Gadd DA;Hillary RF;McCartney DL;Zaghlool SB;Stevenson AJ;Cheng Y;Fawns-Ritchie C;Nangle C;Campbell A;Flaig R;Harris SE;Walker RM;Shi L;Tucker-Drob EM;Gieger C;Peters A;Waldenberger M;Graumann J;McRae AF;Deary IJ;Porteous DJ;Hayward C;Visscher PM;Cox SR;Evans KL;McIntosh AM;Suhre K;Marioni RE
通讯作者：
Marioni RE
影响因子：
3.7
作者：
Allione A;Marcon F;Fiorito G;Guarrera S;Siniscalchi E;Zijno A;Crebelli R;Matullo G
通讯作者：
Matullo G
影响因子：
7.8
作者：
Fiorito G;Caini S;Palli D;Bendinelli B;Saieva C;Ermini I;Valentini V;Assedi M;Rizzolo P;Ambrogetti D;Ottini L;Masala G
通讯作者：
Masala G
DOI：
10.1016/j.numecd.2013.10.026
发表时间：
2014-05-01
影响因子：
3.9
作者：
Fiorito, G.;Guarrera, S.;Matullo, G.
通讯作者：
Matullo, G.
影响因子：
2.3
作者：
Dudbridge F
通讯作者：
Dudbridge F