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

BackgroundPrevious 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...

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Main Authors: Xiaofeng Lv, Zeng Hu, Fangqi Liang, Shanshan Liu, Haiping Gong, Jihang Du, Xinmin Deng, Jun-Hui Qian, Qian Nie, Jian Luo
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Neurology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2023.1178051/full
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author Xiaofeng Lv
Xiaofeng Lv
Zeng Hu
Fangqi Liang
Shanshan Liu
Haiping Gong
Jihang Du
Jihang Du
Xinmin Deng
Jun-Hui Qian
Jun-Hui Qian
Qian Nie
Jian Luo
author_facet Xiaofeng Lv
Xiaofeng Lv
Zeng Hu
Fangqi Liang
Shanshan Liu
Haiping Gong
Jihang Du
Jihang Du
Xinmin Deng
Jun-Hui Qian
Jun-Hui Qian
Qian Nie
Jian Luo
author_sort Xiaofeng Lv
collection DOAJ
description BackgroundPrevious 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.MethodsOur 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.ResultsIn 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.ConclusionsOur 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 doaj.art-3f1bca52774a45758d604d0e273fa2d22023-05-18T07:34:56ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-05-011410.3389/fneur.2023.11780511178051Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysisXiaofeng Lv0Xiaofeng Lv1Zeng Hu2Fangqi Liang3Shanshan Liu4Haiping Gong5Jihang Du6Jihang Du7Xinmin Deng8Jun-Hui Qian9Jun-Hui Qian10Qian Nie11Jian Luo12Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaSchool of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaSchool of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaShenzhen Hospital of Beijing University of Chinese Medicine (Longgang), Shenzhen, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaSchool of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaGuang'an Traditional Chinese Medicine Hospital, Guang'an, Sichuan, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaBackgroundPrevious 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.MethodsOur 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.ResultsIn 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.ConclusionsOur 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.https://www.frontiersin.org/articles/10.3389/fneur.2023.1178051/fullMendelian randomizationischemic strokefrozen shouldergenome-wide association studycausal association
spellingShingle Xiaofeng Lv
Xiaofeng Lv
Zeng Hu
Fangqi Liang
Shanshan Liu
Haiping Gong
Jihang Du
Jihang Du
Xinmin Deng
Jun-Hui Qian
Jun-Hui Qian
Qian Nie
Jian Luo
Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis
Frontiers in Neurology
Mendelian randomization
ischemic stroke
frozen shoulder
genome-wide association study
causal association
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 Mendelian randomization
ischemic stroke
frozen shoulder
genome-wide association study
causal association
url https://www.frontiersin.org/articles/10.3389/fneur.2023.1178051/full
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