Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA.
Clin Epigenetics. 2024 Oct 28;16(1):149. doi: 10.1186/s13148-024-01753-4.
Epigenome-wide association studies have identified multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. This study aimed to test the hypothesis that an alcohol consumption epigenetic risk score (ERS) is associated with blood pressure (BP) traits.
We implemented an ERS based on a previously reported epigenetic signature of 144 alcohol-associated CpGs in meta-analysis of participants of European ancestry. We found a one-unit increment of ERS was associated with eleven drinks of alcohol consumed per day, on average, across several cohorts (p < 0.0001). We 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. Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 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 BP levels, i.e., a one-unit increase in ERS was associated with 0.74 mm Hg (p = 0.002) higher SBP and 0.50 mm Hg (p = 0.0006) higher DBP, but not with HTN. Longitudinal analyses in FHS (n = 3260) and five independent external cohorts (n = 4021) showed that the baseline ERS was not associated with a change in BP over time or with incident HTN.
Our findings demonstrate that the ERS has potential clinical utility in assessing lifestyle factors related to cardiovascular risk, especially when self-reported behavioral data (e.g., alcohol consumption) are unreliable or unavailable.
全基因组关联研究已经确定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。本研究旨在检验以下假设：饮酒表观遗传风险评分（ERS）与血压（BP）特征有关。
我们基于先前报道的 144 个与酒精相关的 CpG 的表观遗传特征，在欧洲血统参与者的荟萃分析中构建了 ERS。我们发现，ERS 每增加一个单位，与平均每天饮用 11 杯酒精有关（p<0.0001）。我们在 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）的关联。FHS 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=4.64E-07），DBP 升高 0.68 毫米汞柱（p=0.006），HTN 的比值比为 1.78（p<2E-16）。对 8 个独立外部队列（n=11544）BP 特征的 ERS 横断面关联的荟萃分析显示了与 BP 水平的相似关系，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），但与 HTN 无关。FHS（n=3260）和 5 个独立外部队列（n=4021）的纵向分析显示，基线 ERS 与随时间推移的 BP 变化或 HTN 的发生无关。
我们的研究结果表明，ERS 在评估与心血管风险相关的生活方式因素方面具有潜在的临床应用价值，尤其是当自我报告的行为数据（例如饮酒）不可靠或不可用时。
