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

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

doi:10.1016/j.numecd.2023.01.018

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

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

Authors

Meng-Jin Hu¹, Song Hu², Jiang-Shan Tan², Yue-Jin Yang³

Affiliations

¹ 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.
² 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.
³ 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. Electronic address: yangyjfw@126.com.

PMID: 36775708
DOI: 10.1016/j.numecd.2023.01.018

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.

Keywords: Cardiovascular diseases; Diabetes; Family history; Genetic variants.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cardiovascular Diseases* / diagnosis
Cardiovascular Diseases* / epidemiology
Cardiovascular Diseases* / genetics
Diabetes Mellitus* / diagnosis
Diabetes Mellitus* / epidemiology
Diabetes Mellitus* / genetics
Genome-Wide Association Study
Humans
Hypertension*
Ischemic Stroke*
Mendelian Randomization Analysis
Myocardial Infarction* / diagnosis
Myocardial Infarction* / epidemiology
Myocardial Infarction* / genetics
Polymorphism, Single Nucleotide