The relationship between alcohol consumption, circulating proteins, and cardiovascular disease (CVD) risk has not been well studied. We performed association analyses of alcohol consumption with three CVD risk factors and 71 CVD-related circulating proteins measured in 6,745 Framingham Heart Study participants (mean age, 49 years; 53% women). We found that an increase in alcohol consumption was associated with a higher risk of incident hypertension (P=7.2E-3) but a lower risk of incident obesity (P=5.7E-4) and type 2 diabetes (P=1.4E-5) in a 14-year of follow-up. Using independent discovery (n=4,348) and validation (n=2,397) samples, we identified 20 alcohol-associated proteins (FDR<0.05 in discovery and P<0.05/n in validation), with majority (18 of 20 proteins) inversely associated with alcohol consumption. The alcohol-protein associations remained similar after removing heavy drinkers. Four proteins demonstrated consistent triangular relationships, as expected, with alcohol consumption and CVD risk factors. For example, a greater level of APOA1, which was associated with a higher alcohol consumption (P=1.2E-65), was associated with a lower risk of type 2 diabetes (P=3.1E-5). However, several others showed inconsistent triangular relationships, e.g., a greater level of GDF15, which was associated with a lower alcohol consumption (P=1.0E-13), was associated with an increased risk of hypertension (P=2.4E-4). In conclusion, we identified 20 alcohol-associated proteins and demonstrated complex relationships between alcohol consumption, circulating proteins and CVD risk factors. Future studies with integration of more proteomic markers and larger sample size are warranted to unravel the complex relationship between alcohol consumption and CVD risk.

中文翻译：

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饮酒与心血管疾病相关的蛋白质组生物标志物

饮酒，循环蛋白和心血管疾病（CVD）风险之间的关系尚未得到很好的研究。我们对6,745名弗雷明汉心脏研究参与者（平均年龄，49岁； 53％的女性）进行了酒精摄入量与三种CVD危险因素和71种CVD相关循环蛋白的关联分析。我们发现，饮酒量增加与发生高血压的风险较高（P = 7.2E-3），但与发生肥胖症的风险较高（P = 5.7E-4）和2型糖尿病（P = 1.4E- 5）在14年的随访中。使用独立的发现（n = 4,348）和验证（n = 2,397）样品，我们鉴定了20种与酒精相关的蛋白质（发现FDR <0.05，验证中P <0.05 / n），其中大部分（20种蛋白质中的18种）反向关联饮酒。去除大量饮酒者后，酒精-蛋白质的关联仍然相似。如预期的那样，四种蛋白质与酒精消耗和CVD危险因素之间显示出一致的三角关系。例如，较高的APOA1水平与较高的酒精消费量相关（P = 1.2E-65），与较低的2型糖尿病风险相关（P = 3.1E-5）。然而，其他一些人则显示出不一致的三角关系，例如，较高的GDF15水平与较低的饮酒量（P = 1.0E-13）相关，与高血压风险增加相关（P = 2.4E-4） 。总之，我们鉴定了20种与酒精相关的蛋白质，并证明了酒精消耗，循环蛋白质和CVD危险因素之间的复杂关系。