Huang Ya, Xu Min, Xie Lan, Wang Tiange, Huang Xiaolin, Lv Xiaofei, Chen Ying, Ding Lin, Lin Lin, Wang Weiqing, Bi Yufang, Sun Yimin, Zhang Yifei, Ning Guang
State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing, 100084, China.
Atherosclerosis. 2016 Apr;247:218-24. doi: 10.1016/j.atherosclerosis.2015.12.034. Epub 2015 Dec 29.
Observational studies showed that obesity is a major risk factor for peripheral arterial disease (PAD). However, conventional epidemiology studies are vulnerable to residual bias from confounding factors. We aimed to explore the causality of obesity in development of PAD using Mendelian Randomization (MR) approach.
A MR analysis was performed in 11,477 community-dwelling adults aged 40 years and above recruited from two nearby communities during 2011-2013 in Shanghai, China. We genotyped 14 body mass index (BMI) associated common variants identified and validated in East Asians. PAD was defined as ankle-to-brachial index (ABI) <0.90 or >1.40. Weighted BMI genetic risk score (GRS) was used as the Instrumental Variable (IV).
After adjusted for confounding factors, we found that each standard deviation (SD, 2.76 points) increase in BMI-GRS was associated with 0.43 (95% confidence interval [CI]: 0.36-0.49) kg/m(2) increase in BMI (P < 0.0001) and an odds ratio (OR) for PAD of 1.17 (95% CI: 1.07-1.27; P = 0.0004). Compared with the lowest quartile of BMI-GRS, the second, third and highest quartile associated with 9%, 19% and 45% increment of PAD risk, respectively (P for trend = 0.002). In the MR analysis, we demonstrated a causal relationship between obesity and PAD (OR = 1.44 per BMI-unit, 95% CI: 1.18-1.75; P = 0.0003).
This study suggested that obesity may be causally associated with PAD after controlling for the potential intermediate factors like hypertension, dyslipidemia and hyperglycemia.
观察性研究表明，肥胖是外周动脉疾病（PAD）的主要危险因素。然而，传统的流行病学研究容易受到混杂因素残留偏倚的影响。我们旨在使用孟德尔随机化（MR）方法探讨肥胖在PAD发生发展中的因果关系。
对2011 - 2013年期间在中国上海两个相邻社区招募的11477名40岁及以上的社区居住成年人进行了MR分析。我们对在东亚人群中鉴定并验证的14个与体重指数（BMI）相关的常见变异进行了基因分型。PAD定义为踝臂指数（ABI）<0.90或>1.40。加权BMI遗传风险评分（GRS）用作工具变量（IV）。
在调整混杂因素后，我们发现BMI - GRS每增加一个标准差（SD，2.76分），BMI增加0.43（95%置信区间[CI]：0.36 - 0.49）kg/m²（P < 0.0001），PAD的比值比（OR）为1.17（95% CI：1.07 - 1.27；P = 0.0004）。与BMI - GRS的最低四分位数相比，第二、第三和最高四分位数分别使PAD风险增加9%、19%和45%（趋势P = 0.002）。在MR分析中，我们证明了肥胖与PAD之间存在因果关系（每BMI单位的OR = 1.44，95% CI：1.18 - 1.75；P = 0.0003）。
本研究表明，在控制高血压、血脂异常和高血糖等潜在中间因素后，肥胖可能与PAD存在因果关联。
