Genetic Association of Waist-to-Hip Ratio With Cardiometabolic Traits, Type 2 Diabetes, and Coronary Heart Disease.
Genetic Association of Waist-to-Hip Ratio With Cardiometabolic Traits, Type 2 Diabetes, and Coronary Heart Disease.
复制标题
腰围比与心脏代谢性状，2型糖尿病和冠状动脉疾病的遗传关联。
DOI：
10.1001/jama.2016.21042
复制
发表时间：
2017-02-14
期刊：
影响因子：
--
通讯作者：
Kathiresan S
中科院分区：
文献类型：
--
作者：
Emdin CA;Khera AV;Natarajan P;Klarin D;Zekavat SM;Hsiao AJ;Kathiresan S
在观察性研究中，腹部肥胖与2型糖尿病和冠心病（CHD）有关。这些关联是否代表因果关系仍不确定。通过血脂、血压和血糖表型的潜在中间体，测试经身体质量指数（WHRadjBMI）调整的腰臀比多基因风险评分与2型糖尿病和冠心病的关系。WHRadjBMI是一种腹部肥胖的测量方法。基于48个单核苷酸多态性构建了WHRadjBMI的多基因风险评分。通过结合病例对照和横断面数据集的孟德尔随机化分析，该评分（腹部肥胖遗传易感性的衡量指标）与心脏代谢特征、2型糖尿病和冠心病的相关性得到了检验。心脏代谢特征的估计是基于一个综合数据集，包括2007年至2015年进行的4项全基因组关联研究的总结结果，其中包括多达322 154名参与者，以及2007年至2011年收集的英国生物银行的个人水平横断面数据，其中包括111 986名个体。2型糖尿病和冠心病的估计来自2007-2015年进行的两项独立全基因组关联研究的汇总统计数据，分别包括149821名个体和184305名个体，并结合英国生物银行的个人水平数据。WHRadjBMI增加的遗传易感性。2型糖尿病和冠心病。在英国生物银行（UK Biobank）的111 986人中，平均年龄为57[标准差（SD） 8]岁，58 845名参与者（52.5%）为女性，平均腰臀比为0.875。对汇总水平全基因组关联研究结果和个体水平UK Biobank数据的分析表明，由多基因风险评分介导的WHRadjBMI每增加一个SD，甘油三酯水平升高27 mg/dl，两小时血糖水平升高4.1 mg/dl，收缩压升高2.1 mm Hg （P≤0.001）。WHRadjBMI基因增加1 SD也与2型糖尿病的高风险相关[OR 1.77 CI 1.57, 2.00；每1000参与者年的绝对风险增加（ARI） 6.0 CI 4.4, 7.8；有2型糖尿病结局的参与者人数，40530人]和冠心病（OR 1.46 CI 1.32, 1.62; ARI 1.8 CI 1.3, 2.4；有冠心病结局的参与者人数，66440人）。经体重指数调整后腰臀比较高的遗传倾向与2型糖尿病和冠心病的风险增加有关。这些结果提供证据支持腹部肥胖与这些结果之间的因果关系。
In observational studies, abdominal adiposity has been associated with type 2 diabetes and coronary heart disease (CHD). Whether these associations represent causal relationships remains uncertain. To test the association of a polygenic risk score for waist-to-hip ratio adjusted for body mass index (WHRadjBMI), a measure of abdominal adiposity, with type 2 diabetes and CHD through the potential intermediates of blood lipids, blood pressure and glycemic phenotypes. A polygenic risk score for WHRadjBMI based on 48 single nucleotide polymorphisms was constructed. The association of this score, a measure of genetic predisposition to abdominal adiposity, with cardiometabolic traits, type 2 diabetes, and CHD was tested in a Mendelian randomization analysis that combined case-control and cross-sectional datasets. Estimates for cardiometabolic traits were based on a combined dataset including summary results from 4 genome-wide association studies conducted from 2007 to 2015, consisting of up to 322 154 participants, as well as individual level, cross sectional data from the UK Biobank collected from 2007–2011, consisting of 111 986 individuals. Estimates for type 2 diabetes and CHD were derived from summary statistics of 2 separate genome-wide association studies conducted from 2007–2015, and including 149 821 individuals and 184 305 individuals, respectively, combined with individual level data from the UK Biobank. Genetic predisposition to increased WHRadjBMI. Type 2 diabetes and CHD. In 111 986 individuals in UK Biobank, the mean age was 57 [standard deviation (SD) 8] years, 58 845 participants (52.5%) were women and the mean waist-to-hip ratio was 0.875. Analysis of summary-level genome-wide association study results and individual-level UK Biobank data demonstrated that a one SD increase in WHRadjBMI mediated by the polygenic risk score was associated with 27 mg/dl higher triglyceride levels, 4.1 mg/dl higher two-hour glucose levels, and 2.1 mm Hg higher systolic blood pressure (each P ≤ 0.001). A one SD genetic increase in WHRadjBMI was also associated with a higher risk of type 2 diabetes [OR 1.77 CI 1.57, 2.00; absolute risk increase per 1000 participant years (ARI) 6.0 CI 4.4, 7.8; number of participants with type 2 diabetes outcome, 40 530] and CHD (OR 1.46 CI 1.32, 1.62; ARI 1.8 CI 1.3, 2.4; number of participants with CHD outcome, 66 440). A genetic predisposition to higher waist-to-hip ratio adjusted for body mass index was associated with increased risk of type 2 diabetes and coronary heart disease. These results provide evidence supportive of a causal association between abdominal adiposity and these outcomes.