个体或家族性糖尿病与八种心血管疾病的关系：一项双样本孟德尔随机化研究。

Individual or familial diabetes in relation to eight cardiovascular diseases: A two-sample Mendelian randomization study.

作者信息

Hu Meng-Jin, Hu Song, Tan Jiang-Shan, Yang Yue-Jin

机构信息

Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, China.

出版信息

Nutr Metab Cardiovasc Dis. 2023 Apr;33(4):883-891. doi: 10.1016/j.numecd.2023.01.018. Epub 2023 Jan 29.

DOI:10.1016/j.numecd.2023.01.018

PMID:36775708

Abstract

BACKGROUND AND AIMS

Diabetes is associated with increased risk of certain cardiovascular diseases, yet the causality remains to be determined. Meanwhile, given that first-degree relatives share 50% of genes, the effect of familial diabetes is also worthy of attention. Therefore, we sought to investigate the causal relations of individual or familial diabetes with eight cardiovascular diseases, including myocardial infarction, hypertension, atrial fibrillation, heart failure, cardiac death, pulmonary embolism, transient ischemic attack, and ischemic stroke.

METHODS AND RESULTS

Applying two-sample Mendelian randomization, we selected instruments for genetic predisposition to individual or familial diabetes based on published genome-wide association studies. The primary analyses were conducted using the random-effects inverse-variance weighted method. We found that genetically predicted individual diabetes was causally associated with higher risks of myocardial infarction (odd ratio [OR] = 1.09; 95% confidence interval [CI]: 1.05-1.13; P < 0.0001), hypertension (OR = 1.08; 95% CI: 1.03-1.13; P = 0.0006), and ischemic stroke (OR = 1.10; 95% CI: 1.05-1.15; P < 0.0001). Genetically predicted paternal diabetes could increase the risk of ischemic stroke (OR = 1.16; 95% CI: 1.04-1.30; P = 0.0061). Genetically predicted maternal diabetes could increase the risk of myocardial infarction (OR = 1.18; 95% CI: 1.09-1.29; P = 0.0001). Genetically predicted siblings' diabetes was causally associated with higher risks of myocardial infarction (OR = 1.17; 95% CI: 1.08-1.27; P = 0.0001) and hypertension (OR = 1.19; 95% CI: 1.06-1.34; P = 0.0036). No significant differences were observed in other outcomes.

CONCLUSION

This study supports causal effects of not only individual but also familial diabetes on the development of cardiovascular diseases, which will help realize the potential effect of family history in the prevention of cardiovascular diseases.

摘要

背景与目的

糖尿病与某些心血管疾病风险增加相关，但因果关系仍有待确定。同时，鉴于一级亲属共享50%的基因，家族性糖尿病的影响也值得关注。因此，我们试图研究个体或家族性糖尿病与八种心血管疾病之间的因果关系，这八种疾病包括心肌梗死、高血压、心房颤动、心力衰竭、心源性死亡、肺栓塞、短暂性脑缺血发作和缺血性中风。

方法与结果

应用两样本孟德尔随机化方法，我们基于已发表的全基因组关联研究选择个体或家族性糖尿病遗传易感性的工具变量。主要分析采用随机效应逆方差加权法。我们发现，基因预测的个体糖尿病与心肌梗死风险升高存在因果关系（比值比[OR]=1.09；95%置信区间[CI]：1.05-1.13；P<0.0001）、高血压（OR=1.08；95%CI：1.03-1.13；P=0.00０6）和缺血性中风（OR=1.10；95%CI：1.05-1.15；P<0.0001）。基因预测的父系糖尿病可增加缺血性中风风险（OR=1.16；95%CI：1.04-1.30；P=0.0061）。基因预测的母系糖尿病可增加心肌梗死风险（OR=1.18；95%CI：1.09-1.29；P=0.0001）。基因预测的兄弟姐妹糖尿病与心肌梗死风险升高存在因果关系（OR=1.17；95%CI：1.08-1.27；P=0.0001）和高血压（OR=1.１9；95%CI：1.06-1.34；P=0.0036）。其他结局未观察到显著差异。