Linking Cortical Structure and Cerebrospinal Fluid Metabolites with Venous Thromboembolism Risk: A Two-Step Mendelian Randomization and Co-Localization Analysis

Background Venous thromboembolism (VTE) is a complex vascular disorder, and emerging research suggests potential neurovascular and metabolic factors in its pathogenesis. However, the specific roles of cortical structure features and cerebrospinal fluid (CSF) metabolites in VTE risk remain underexplo...

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Main Authors: Tianni Liu MD, Junxian Li MS, Qiong Liu MD, Guojun Liang MD
Format: Article
Language:English
Published: SAGE Publishing 2025-07-01
Series:Clinical and Applied Thrombosis/Hemostasis
Online Access:https://doi.org/10.1177/10760296251360018
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author Tianni Liu MD
Junxian Li MS
Qiong Liu MD
Guojun Liang MD
author_facet Tianni Liu MD
Junxian Li MS
Qiong Liu MD
Guojun Liang MD
author_sort Tianni Liu MD
collection DOAJ
description Background Venous thromboembolism (VTE) is a complex vascular disorder, and emerging research suggests potential neurovascular and metabolic factors in its pathogenesis. However, the specific roles of cortical structure features and cerebrospinal fluid (CSF) metabolites in VTE risk remain underexplored. Methods Using Mendelian randomization (MR) analysis, we examined associations between cortical features, CSF metabolites and VTE. Mediation MR and co-localization analyses were employed to explore genetic pathways and potential mediatory effects. Results MR analysis initially identified associations between six cortical features and fifteen CSF metabolites with VTE. After false discovery rate (FDR) correction, lingual gyrus thickness remained statistically significant, while isoleucine and methylmalonate showed suggestive associations. Mediation MR analysis revealed no causal relationship between lingual gyrus thickness and the CSF metabolites isoleucine or methylmalonate. Co-localization analysis indicated low posterior probabilities for shared genetic variants, suggesting that these traits influence venous thromboembolism (VTE) through distinct biological mechanisms. Conclusion The findings suggest that MRI-based cortical structure features and CSF profiling hold potential as complementary tools for assessing VTE risk. Further research is warranted to investigate the neurovascular and metabolic mechanisms underlying VTE.
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spelling doaj-art-c57d4c1bf2cf499ea0c3c9ef51550ac42025-08-20T02:40:58ZengSAGE PublishingClinical and Applied Thrombosis/Hemostasis1938-27232025-07-013110.1177/10760296251360018Linking Cortical Structure and Cerebrospinal Fluid Metabolites with Venous Thromboembolism Risk: A Two-Step Mendelian Randomization and Co-Localization AnalysisTianni Liu MD0Junxian Li MS1Qiong Liu MD2Guojun Liang MD3 , Guangzhou, Guangdong, China Guangzhou Red Cross Hospital No.396 Tongfu Middle Road, Guangzhou, Guangdong, China Huadu District People's Hospital of Guangzhou, Guangzhou, Guangdong, China Huadu District People's Hospital of Guangzhou, Guangzhou, Guangdong, ChinaBackground Venous thromboembolism (VTE) is a complex vascular disorder, and emerging research suggests potential neurovascular and metabolic factors in its pathogenesis. However, the specific roles of cortical structure features and cerebrospinal fluid (CSF) metabolites in VTE risk remain underexplored. Methods Using Mendelian randomization (MR) analysis, we examined associations between cortical features, CSF metabolites and VTE. Mediation MR and co-localization analyses were employed to explore genetic pathways and potential mediatory effects. Results MR analysis initially identified associations between six cortical features and fifteen CSF metabolites with VTE. After false discovery rate (FDR) correction, lingual gyrus thickness remained statistically significant, while isoleucine and methylmalonate showed suggestive associations. Mediation MR analysis revealed no causal relationship between lingual gyrus thickness and the CSF metabolites isoleucine or methylmalonate. Co-localization analysis indicated low posterior probabilities for shared genetic variants, suggesting that these traits influence venous thromboembolism (VTE) through distinct biological mechanisms. Conclusion The findings suggest that MRI-based cortical structure features and CSF profiling hold potential as complementary tools for assessing VTE risk. Further research is warranted to investigate the neurovascular and metabolic mechanisms underlying VTE.https://doi.org/10.1177/10760296251360018
spellingShingle Tianni Liu MD
Junxian Li MS
Qiong Liu MD
Guojun Liang MD
Linking Cortical Structure and Cerebrospinal Fluid Metabolites with Venous Thromboembolism Risk: A Two-Step Mendelian Randomization and Co-Localization Analysis
Clinical and Applied Thrombosis/Hemostasis
title Linking Cortical Structure and Cerebrospinal Fluid Metabolites with Venous Thromboembolism Risk: A Two-Step Mendelian Randomization and Co-Localization Analysis
title_full Linking Cortical Structure and Cerebrospinal Fluid Metabolites with Venous Thromboembolism Risk: A Two-Step Mendelian Randomization and Co-Localization Analysis
title_fullStr Linking Cortical Structure and Cerebrospinal Fluid Metabolites with Venous Thromboembolism Risk: A Two-Step Mendelian Randomization and Co-Localization Analysis
title_full_unstemmed Linking Cortical Structure and Cerebrospinal Fluid Metabolites with Venous Thromboembolism Risk: A Two-Step Mendelian Randomization and Co-Localization Analysis
title_short Linking Cortical Structure and Cerebrospinal Fluid Metabolites with Venous Thromboembolism Risk: A Two-Step Mendelian Randomization and Co-Localization Analysis
title_sort linking cortical structure and cerebrospinal fluid metabolites with venous thromboembolism risk a two step mendelian randomization and co localization analysis
url https://doi.org/10.1177/10760296251360018
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