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Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis

BACKGROUND: Previous epidemiological and other studies have shown an association between ischemic stroke (IS) and frozen shoulder (FS). However, the causal relationship between them remains unclear. Therefore, the present study aimed to investigate the causal relationship between IS and FS using a t...

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Autores principales: Lv, Xiaofeng, Hu, Zeng, Liang, Fangqi, Liu, Shanshan, Gong, Haiping, Du, Jihang, Deng, Xinmin, Qian, Jun-Hui, Nie, Qian, Luo, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233007/
https://www.ncbi.nlm.nih.gov/pubmed/37273710
http://dx.doi.org/10.3389/fneur.2023.1178051
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author Lv, Xiaofeng
Hu, Zeng
Liang, Fangqi
Liu, Shanshan
Gong, Haiping
Du, Jihang
Deng, Xinmin
Qian, Jun-Hui
Nie, Qian
Luo, Jian
author_facet Lv, Xiaofeng
Hu, Zeng
Liang, Fangqi
Liu, Shanshan
Gong, Haiping
Du, Jihang
Deng, Xinmin
Qian, Jun-Hui
Nie, Qian
Luo, Jian
author_sort Lv, Xiaofeng
collection PubMed
description BACKGROUND: Previous epidemiological and other studies have shown an association between ischemic stroke (IS) and frozen shoulder (FS). However, the causal relationship between them remains unclear. Therefore, the present study aimed to investigate the causal relationship between IS and FS using a two-sample Mendelian randomization method. METHODS: Our research was divided into two stages: discovery and replication. The data were extracted from publicly available genome-wide association studies (GWAS). We selected a large sample of IS (n = 440, 328) and its subtypes (large-artery atherosclerotic stroke (LAS), cardioembolic stroke (CES), and stroke caused by small-vessel disease (SVS) and lacunar stroke (n = 254, 959) as exposure data. Additionally, we selected a large sample of FS as outcome data (n = 451, 099). Inverse variance weighting (IVW) was applied as the primary analysis method. The weighted median, MR-Egger, simple model, and weighted model were used as complementary analysis methods to assess causal effects. Moreover, heterogeneity was analyzed using Cochran's Q-test with IVW and MR-Egger. The MR-Egger intercept and MR-PRESSO analysis methods were used for pleiotropy testing. The stability of the results was also assessed using a leave-one-out analysis. RESULTS: In the discovery stage, the IVW approach revealed an odds ratio (OR) of 1.207 with a 95% confidence interval (CI) of 1.027–1.417 and a P-value of 0.022. This suggests a causal association between IS levels and an increased risk of FS. In the subtype studies of IS, the findings were negative. However, during the replication stage, a significant causal link was found between selected lacunar strokes and FS with an OR of 1.252, a 95% CI of 1.105–1.419, and a P-value of 0.0004. All studies had no pleiotropy or heterogeneity, and the findings were robust. CONCLUSIONS: Our study confirmed the causal relationship between any IS level and increased risk of FS. Furthermore, the same results were obtained in the replication stage with lacunar stroke as an exposure factor. However, there was no direct causal relationship between the subtypes of IS and FS. Our study provides theoretical support for shoulder care for patients with IS.
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spelling pubmed-102330072023-06-02 Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis Lv, Xiaofeng Hu, Zeng Liang, Fangqi Liu, Shanshan Gong, Haiping Du, Jihang Deng, Xinmin Qian, Jun-Hui Nie, Qian Luo, Jian Front Neurol Neurology BACKGROUND: Previous epidemiological and other studies have shown an association between ischemic stroke (IS) and frozen shoulder (FS). However, the causal relationship between them remains unclear. Therefore, the present study aimed to investigate the causal relationship between IS and FS using a two-sample Mendelian randomization method. METHODS: Our research was divided into two stages: discovery and replication. The data were extracted from publicly available genome-wide association studies (GWAS). We selected a large sample of IS (n = 440, 328) and its subtypes (large-artery atherosclerotic stroke (LAS), cardioembolic stroke (CES), and stroke caused by small-vessel disease (SVS) and lacunar stroke (n = 254, 959) as exposure data. Additionally, we selected a large sample of FS as outcome data (n = 451, 099). Inverse variance weighting (IVW) was applied as the primary analysis method. The weighted median, MR-Egger, simple model, and weighted model were used as complementary analysis methods to assess causal effects. Moreover, heterogeneity was analyzed using Cochran's Q-test with IVW and MR-Egger. The MR-Egger intercept and MR-PRESSO analysis methods were used for pleiotropy testing. The stability of the results was also assessed using a leave-one-out analysis. RESULTS: In the discovery stage, the IVW approach revealed an odds ratio (OR) of 1.207 with a 95% confidence interval (CI) of 1.027–1.417 and a P-value of 0.022. This suggests a causal association between IS levels and an increased risk of FS. In the subtype studies of IS, the findings were negative. However, during the replication stage, a significant causal link was found between selected lacunar strokes and FS with an OR of 1.252, a 95% CI of 1.105–1.419, and a P-value of 0.0004. All studies had no pleiotropy or heterogeneity, and the findings were robust. CONCLUSIONS: Our study confirmed the causal relationship between any IS level and increased risk of FS. Furthermore, the same results were obtained in the replication stage with lacunar stroke as an exposure factor. However, there was no direct causal relationship between the subtypes of IS and FS. Our study provides theoretical support for shoulder care for patients with IS. Frontiers Media S.A. 2023-05-18 /pmc/articles/PMC10233007/ /pubmed/37273710 http://dx.doi.org/10.3389/fneur.2023.1178051 Text en Copyright © 2023 Lv, Hu, Liang, Liu, Gong, Du, Deng, Qian, Nie and Luo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Lv, Xiaofeng
Hu, Zeng
Liang, Fangqi
Liu, Shanshan
Gong, Haiping
Du, Jihang
Deng, Xinmin
Qian, Jun-Hui
Nie, Qian
Luo, Jian
Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis
title Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis
title_full Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis
title_fullStr Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis
title_full_unstemmed Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis
title_short Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis
title_sort causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample mendelian randomization analysis
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233007/
https://www.ncbi.nlm.nih.gov/pubmed/37273710
http://dx.doi.org/10.3389/fneur.2023.1178051
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