Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland.
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow Scotland.
JAMA Cardiol. 2017 Aug 1;2(8):882-889. doi: 10.1001/jamacardio.2016.5804.
IMPORTANCE: Higher body mass index (BMI) is a risk factor for cardiometabolic disease; however, the underlying causal associations remain unclear. OBJECTIVES: To use UK Biobank data to report causal estimates of the association between BMI and cardiometabolic disease outcomes and traits, such as pulse rate, using mendelian randomization. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional baseline data from a population-based cohort study including 119 859 UK Biobank participants with complete phenotypic (medical and sociodemographic) and genetic data. Participants attended 1 of 22 assessment centers across the United Kingdom between 2006 and 2010. The present study was conducted from May 1 to July 11, 2016. MAIN OUTCOMES AND MEASURES: Prevalence of hypertension, coronary heart disease, and type 2 diabetes were determined at assessment, based on self-report. Blood pressure was measured clinically. Participants self-reported sociodemographic information pertaining to relevant confounders. A polygenic risk score comprising 93 single-nucleotide polymorphisms associated with BMI from previous genome-wide association studies was constructed, and the genetic risk score was applied to derive causal estimates using a mendelian randomization approach. RESULTS: Of the 119 859 individuals included in the study, 56 816 (47.4%) were men; mean (SD) age was 56.87 (7.93) years. Mendelian randomization analysis showed significant positive associations between genetically instrumented higher BMI and risk of hypertension (odds ratio [OR] per 1-SD higher BMI, 1.64; 95% CI, 1.48-1.83; P = 1.1 × 10-19), coronary heart disease (OR, 1.35; 95% CI, 1.09-1.69; P = .007) and type 2 diabetes (OR, 2.53; 95% CI, 2.04-3.13; P = 1.5 × 10-17), as well as systolic blood pressure (β = 1.65 mm Hg; 95% CI, 0.78-2.52 mm Hg; P = 2.0 × 10-04) and diastolic blood pressure (β = 1.37 mm Hg; 95% CI, 0.88-1.85 mm Hg; P = 3.6 × 10-08). These associations were independent of age, sex, Townsend deprivation scores, alcohol intake, and smoking history. CONCLUSIONS AND RELEVANCE: The results of this study add to the burgeoning evidence of an association between higher BMI and increased risk of cardiometabolic diseases. This finding has relevance for public health policies in many countries with increasing obesity levels.
重要提示:较高的体重指数(BMI)是心血管代谢疾病的危险因素;然而,其潜在的因果关系仍不清楚。
目的:利用英国生物库的数据,采用孟德尔随机化报告 BMI 与心血管代谢疾病结局以及脉搏率等特征之间的因果关联的估计值。
设计、地点和参与者:本研究为一项基于人群的队列研究的横断面基线数据,纳入了 119859 名具有完整表型(医疗和社会人口统计学)和遗传数据的英国生物库参与者。参与者于 2006 年至 2010 年间在英国的 22 个评估中心中的 1 个参加了评估。本研究于 2016 年 5 月 1 日至 7 月 11 日进行。
主要结局和测量指标:根据自我报告,在评估时确定高血压、冠心病和 2 型糖尿病的患病率。血压通过临床测量。参与者自我报告了与相关混杂因素有关的社会人口统计学信息。构建了一个由 93 个单核苷酸多态性组成的多基因风险评分,这些单核苷酸多态性与之前的全基因组关联研究中的 BMI 相关,采用孟德尔随机化方法应用遗传风险评分来推导出因果估计值。
结果:在纳入的 119859 名个体中,56816 名(47.4%)为男性;平均(标准差)年龄为 56.87(7.93)岁。孟德尔随机化分析显示,较高的 BMI 与高血压(每增加 1-SD BMI 的比值比[OR],1.64;95%CI,1.48-1.83;P = 1.1×10-19)、冠心病(OR,1.35;95%CI,1.09-1.69;P = .007)和 2 型糖尿病(OR,2.53;95%CI,2.04-3.13;P = 1.5×10-17)风险呈显著正相关,还与收缩压(β=1.65mmHg;95%CI,0.78-2.52mmHg;P = 2.0×10-04)和舒张压(β=1.37mmHg;95%CI,0.88-1.85mmHg;P = 3.6×10-08)呈正相关。这些关联独立于年龄、性别、汤森剥夺评分、饮酒量和吸烟史。
结论和相关性:本研究结果增加了较高 BMI 与心血管代谢疾病风险增加之间存在关联的证据。这一发现与许多肥胖水平不断上升的国家的公共卫生政策有关。
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