Bui Helena, Keshawarz Amena, Wang Mengyao, Lee Mikyeong, Ratliff Scott M, Lin Lisha, Birditt Kira S, Faul Jessica D, Peters Annette, Gieger Christian, Delerue Thomas, Kardia Sharon L R, Zhao Wei, Guo Xiuqing, Yao Jie, Rotter Jerome I, Li Yi, Liu Xue, Liu Dan, Tavares Juliana F, Pehlivan Gökhan, Breteler Monique M B, Karabegovic Irma, Ochoa-Rosales Carolina, Voortman Trudy, Ghanbari Mohsen, van Meurs Joyce B J, Nasr Mohamed Kamal, Dörr Marcus, Grabe Hans J, London Stephanie J, Teumer Alexander, Waldenberger Melanie, Weir David R, Smith Jennifer A, Levy Daniel, Ma Jiantao, Liu Chunyu
Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Framingham Heart Study, Framingham, MA, USA.
medRxiv. 2024 Apr 11:2024.02.29.24303545. doi: 10.1101/2024.02.29.24303545.
Epigenome-wide association studies have revealed multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases.
We generated an alcohol consumption epigenetic risk score (ERS) based on previously reported 144 alcohol-associated CpGs and examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. We found an association of alcohol intake with the ERS in the meta-analysis with 0.09 units higher ERS per drink consumed per day ( < 0.0001). Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP ( = 4.64E-07), 0.68 mm Hg higher DBP ( = 0.006), and an odds ratio of 1.78 for HTN ( < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with blood pressure levels, i.e., a one-unit increase in ERS was associated with 0.74 ( = 0.002) and 0.50 ( = 0.0006) mm Hg higher SBP and DBP, but could not confirm the association with hypertension. Longitudinal analyses in FHS (n = 3,260) and five independent external cohorts (n = 4,021) showed that the baseline ERS was not associated with a change in blood pressure over time or with incident HTN.
Our findings provide proof-of-concept that utilizing an ERS is a useful approach to capture the recent health consequences of lifestyle behaviors such as alcohol consumption.
全表观基因组关联研究已经揭示了多个与饮酒相关的DNA甲基化位点（CpG），饮酒是心血管疾病的一个重要生活方式风险因素。
我们基于先前报道的144个与酒精相关的CpG生成了一个饮酒表观遗传风险评分（ERS），并在3898名弗雷明汉心脏研究（FHS）参与者中检验了ERS与收缩压（SBP）、舒张压（DBP）和高血压（HTN）之间的关联。我们在荟萃分析中发现饮酒与ERS存在关联，即每天每多饮用一个酒精单位，ERS升高0.09单位（P<0.0001）。FHS中的横断面分析显示，ERS每增加一个单位，SBP升高1.93毫米汞柱（P = 4.64×10⁻⁷），DBP升高0.68毫米汞柱（P = 0.006），患HTN的比值比为1.78（P<2×10⁻¹⁶）。对8个独立外部队列（n = 11544）中ERS与血压特征的横断面关联进行的荟萃分析显示，与血压水平存在相似关系，即ERS每增加一个单位，SBP升高0.74毫米汞柱（P = 0.002），DBP升高0.50毫米汞柱（P = 0.0006），但无法证实与高血压的关联。FHS（n = 3260）和5个独立外部队列（n = 4021）中的纵向分析表明，基线ERS与血压随时间的变化或与HTN发病无关。
我们的研究结果提供了概念验证，即利用ERS是一种有用的方法，可用于捕捉饮酒等生活方式行为对近期健康的影响。
