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Comprehensive Investigation of Circulating Biomarkers and Their Causal Role in Atherosclerosis-Related Risk Factors and Clinical Events

机译:全面调查的循环生物标志物及其因果作用Atherosclerosis-Related和临床危险因素事件

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BACKGROUND: Circulating biomarkers have been previously associated with atherosclerosis-related risk factors, but the nature of these associations is incompletely understood. METHODS: We performed multivariable-adjusted regressions and 2-sample Mendelian randomization analyses to assess observational and causal associations of 27 circulating biomarkers with 7 cardiovascular traits in up to 451 933 participants of the UK Biobank. RESULTS: After multiple-testing correction (alpha=1.3x10-4), we found a total of 15, 9, 21, 22, 26, 24, and 26 biomarkers strongly associated with coronary artery disease, ischemic stroke, atrial fibrillation, type 2 diabetes, systolic blood pressure, body mass index, and waist-to-hip ratio; respectively. The Mendelian randomization analyses confirmed strong evidence of previously suggested causal associations for several glucose- and lipid-related biomarkers with type 2 diabetes and coronary artery disease. Particularly interesting findings included a protective role of IGF-1 (insulin-like growth factor 1) in systolic blood pressure, and the strong causal association of lipoprotein(a) in coronary artery disease development (p, -0.13; per SD change in exposure and outcome and odds ratio, 1.28; P=2.6x10-4 and P=7.4x10 5, respectively). In addition, our results indicated a causal role of increased ALT (alanine aminotransferase) in the development of type 2 diabetes and hypertension (odds ratio, 1.59 and p, 0.06, per SD change in exposure and outcome; P=4.8x10 and P=6.0x10-5). Our results suggest that it is unlikely that CRP (C-reactive protein) and vitamin D play causal roles of any meaningful magnitude in development of cardiometabolic disease. CONCLUSIONS: We confirmed and extended known associations and reported several novel causal associations providing important insights about the cause of these diseases, which can help accelerate new prevention strategies.
机译:背景:循环生物标志物此前与atherosclerosis-related风险因素,但是这些联系是不完全的性质理解。multivariable-adjusted回归和2-sample孟德尔随机化分析评估观察和因果关联的27所示循环与7心血管生物标记特征在451英国的933名参与者生物。修正(α= 1.3 x10-4),我们发现的26日,15日,9日,21日,22日,24日和26日强烈生物标志物与冠状动脉疾病,缺血性中风中风、心房纤颤、2型糖尿病、收缩压、身体质量指数和腰臀比;随机分析证实了强有力的证据先前提出的因果关联一些葡萄糖,lipid-related生物标记2型糖尿病和冠心病。包括一个特别有趣的发现保护作用的igf - 1(胰岛素样生长因素1)收缩压,强烈的因果关联的脂蛋白(a)冠状动脉疾病发展(p, -0.13;/ SD暴露和结果和概率的变化比,1.28;分别)。一个因果的作用增加了ALT(丙氨酸转氨酶)2型的发展糖尿病和高血压(优势比,1.59和0.06, p / SD曝光和变化的结果;P = 4.8 x10和P = 6.0 x10-5)。不太可能c反应蛋白(c反应蛋白)和维生素D因果任何有意义的角色级在代谢疾病的发展疾病。协会和一些新颖的报道因果关系提供重要的见解对这些疾病的原因,它可以帮助加速新的预防策略。

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