Huan Cai1, Biyang Cai2, Zhonghua Liu1, Wenjun Wu3, Dihong Chen3, Liang Fang1, Liyi Chen1, Wen Sun4, Jialin Liang5, Hao Zhang6. 1. Department of Rehabilitation, Zhongshan City People's Hospital, Zhongshan, 528403, Guangdong, China. 2. Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China. 3. Department of Neurology, Zhongshan City People's Hospital, Zhongshan, 528403, Guangdong, China. 4. Division of Life Sciences and Medicine, Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, China. 5. Department of Endocrinology and Metabolism, Zhongshan City People's Hospital, Zhongshan, 528403, Guangdong, China. jialin_endo@163.com. 6. Department of Neurology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China. zh_hao_neurol@163.com.
Abstract
BACKGROUND AND PURPOSE: Considerable studies have reported inconsistent relationships between ischemic stroke and a large number of factors. These uncertainties may reflect the susceptibility to confounding in observational studies. We aimed to assess genetic correlations and causal relationships between ischemic stroke and diverse phenotypes. METHODS: Summary-level data for ischemic stroke (34,217 cases and 406,111 controls) from the MEGASTROKE consortium were used as the outcome. Exposures were derived from two GWAS statistics curated databases. We explored the genetic correlations and causalities between hundreds of traits and ischemic stroke, using linkage disequilibrium score regression and Mendelian randomization (MR), respectively. Multiple sensitivity analyses were also performed. RESULTS: Genetic correlation analyses reflected genetic overlaps between ischemic stroke and physical activity, cardiometabolic factors, smoking, and lung function. Applying MR, we found suggestive evidence that genetic predisposition to higher concentration of low-density lipoprotein particles (LDL.P) and cholesterol carried in different sizes of LDL.P (LDL.C) were associated with higher risk of ischemic stroke, particular large artery stroke. The strongest effect was observed for small LDL.P in large artery stroke (OR 1.31, 95% CI 1.09-1.56, p = 0.003). The results were overall robust for sensitivity analyses. We further observed significant positive associations of genetically predicted LDL.P and LDL.C with coronary artery disease and myocardial infarction. CONCLUSIONS: Shared genetic overlaps might exist between ischemic stroke and physical activity, cardiometabolic factors, smoking, and lung function. We provided suggestive evidence for a potential causal role of LDL.P and LDL.C in ischemic stroke, particularly in large artery stroke. Future researches are required to confirm these findings.
BACKGROUND AND PURPOSE: Considerable studies have reported inconsistent relationships between ischemic stroke and a large number of factors. These uncertainties may reflect the susceptibility to confounding in observational studies. We aimed to assess genetic correlations and causal relationships between ischemic stroke and diverse phenotypes. METHODS: Summary-level data for ischemic stroke (34,217 cases and 406,111 controls) from the MEGASTROKE consortium were used as the outcome. Exposures were derived from two GWAS statistics curated databases. We explored the genetic correlations and causalities between hundreds of traits and ischemic stroke, using linkage disequilibrium score regression and Mendelian randomization (MR), respectively. Multiple sensitivity analyses were also performed. RESULTS: Genetic correlation analyses reflected genetic overlaps between ischemic stroke and physical activity, cardiometabolic factors, smoking, and lung function. Applying MR, we found suggestive evidence that genetic predisposition to higher concentration of low-density lipoprotein particles (LDL.P) and cholesterol carried in different sizes of LDL.P (LDL.C) were associated with higher risk of ischemic stroke, particular large artery stroke. The strongest effect was observed for small LDL.P in large artery stroke (OR 1.31, 95% CI 1.09-1.56, p = 0.003). The results were overall robust for sensitivity analyses. We further observed significant positive associations of genetically predicted LDL.P and LDL.C with coronary artery disease and myocardial infarction. CONCLUSIONS: Shared genetic overlaps might exist between ischemic stroke and physical activity, cardiometabolic factors, smoking, and lung function. We provided suggestive evidence for a potential causal role of LDL.P and LDL.C in ischemic stroke, particularly in large artery stroke. Future researches are required to confirm these findings.
Authors: Junfen Fan; Madeline Saft; Nadia Sadanandan; Bella Gonzales-Portillo; You Jeong Park; Paul R Sanberg; Cesario V Borlongan; Yumin Luo Journal: Front Aging Neurosci Date: 2020-10-19 Impact factor: 5.750
Authors: Aleksandra Ekkert; Aleksandra Šliachtenko; Julija Grigaitė; Birutė Burnytė; Algirdas Utkus; Dalius Jatužis Journal: Genes (Basel) Date: 2021-12-24 Impact factor: 4.096