Visceral Adiposity and Risk of Stroke: A Mendelian Randomization Study

Ran Xu; Xinzhi Hu; Tao Wang; Yutong Yang; Nan Jiang; Jichang Luo; Xiao Zhang; Aman B Patel; Adam A Dmytriw; Liqun Jiao

doi:10.3389/fneur.2022.804851

Visceral Adiposity and Risk of Stroke: A Mendelian Randomization Study

Front Neurol. 2022 Apr 11:13:804851. doi: 10.3389/fneur.2022.804851. eCollection 2022.

Authors

Ran Xu^{1

2}, Xinzhi Hu³, Tao Wang^{1

2}, Yutong Yang⁴, Nan Jiang^{1

2}, Jichang Luo^{1

2}, Xiao Zhang^{1

2}, Aman B Patel⁵, Adam A Dmytriw^{5

6}, Liqun Jiao^{1

2

7}

Affiliations

¹ Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
² China International Neuroscience Institute (China-INI), Beijing, China.
³ Department of Human Anatomy, Histology and Embryology, Peking Union Medical College Hospital, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
⁴ Faculty of Medicine, Imperial College London, National Heart and Lung Institute, London, United Kingdom.
⁵ Neuroendovascular Program, Massachusetts General Hospital, Boston, MA, United States.
⁶ Neuroradiology and Neurointervention Service, Brigham and Women's Hospital Harvard Medical School, Boston, MA, United States.
⁷ Department of Interventional Neuroradiology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Abstract

Purpose: In recent years, metabolic syndrome has risen in prevalence and brought a heavy disease burden to modern society. As the representative aspect of metabolic syndrome, obesity has been shown to be related to an increased risk of stroke. Given that visceral adipose tissue (VAT) forms the fundamental basis of central obesity, we sought to explore a causal relationship between VAT and stroke by using mendelian randomization (MR) methods.

Methods: Based on two large genome-wide association studies (GWAS) including 325,153 and 35,762 cases of VAT and stroke, respectively, we conducted a MR study which has the inherent advantage of reducing the noise of confounding and reverse causation.

Results: VAT had a significant causal association with ischemic stroke (OR, per 1kg increase in VAT mass, 1.30; 95% CI, 1.18 ~ 1.45; P = 5.87E-07) as opposed to intracranial hemorrhage (ICH) (OR, 1.15; 95% CI, 0.70 ~ 1.88, P = 5.81E-01) as evaluated with inverse-variance weighting (IVW). Regarding subtypes of ischemic stroke, there was a significant causal effect for cardioembolic stroke (OR, 1.34; 95% CI, 1.13 ~ 1.58, P = 8.07E-04), and potential causal effect for small-vessel stroke (OR, 1.32; 95% CI, 1.06 ~ 1.65, P = 1.39E-02) and large-artery atherosclerotic stroke (OR, 1.33; 95% CI, 1.03 ~ 1.70, P = 2.59E-02).

Conclusions: This study provides potential evidence for a causal role of VAT in ischemic stroke and could suggest novel genetical therapeutic strategies for distinct subtypes of ischemic stroke.

Keywords: intracranial hemorrhage (ICH); ischemic stroke; mendelian randomization (MR); single nucleotide polymorphism (SNP); visceral adipose tissue (VAT).