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Causal relationship between genetically determined plasma metabolites and stroke: A two sample Mendelian randomization study.
Huang, Yi; Chen, Siqi; Zhang, Enhao; Han, Liyuan.
Afiliación
  • Huang Y; Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang 315010, China.
  • Chen S; Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang 315010, China.
  • Zhang E; Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang 315010, China.
  • Han L; Center for Cardiovascular and Cerebrovascular Epidemiology and Translational Medicine, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315000, China. Electronic address: hanliyuan@ucas.ac.cn.
Prog Neuropsychopharmacol Biol Psychiatry ; 135: 111133, 2024 Dec 20.
Article en En | MEDLINE | ID: mdl-39222903
ABSTRACT

INTRODUCTION:

This study investigates the causal relationship between plasma metabolites and stroke.

METHOD:

The primary analytical approach employed was the inverse variance weighted (IVW) method, complemented by the weighted median (WM) and MR Egger methods for Additionally, validation of the identified plasma metabolites was performed using the Steiger test and LD linkage disequilibrium score. Furthermore, the main results were confirmed through data from the UK Biobank.

RESULT:

The IVW analysis revealed the most notable negative association found in X-17335 levels (OR [95 % CI] 0.82 [0.72, 0.94]). On the other hand, the strongest positive effect was seen in the 5'-homophase (AMP) to phase ratio (OR [95 % CI] 1.17 [1.03, 1.32]). Moving on to the validation dataset, the most significant positive effect was observed in the 13 HODE+9-HODE levels (OR [95 % CI] 0.996 [0.993, 0.999]), whereas the most significant negative effect was seen in the Dihydroxide levels (OR [95 % CI] 1.004 [1.00, 1.007]). Notably, Alpha ketoglutarate levels exhibited strong causal effects in both datasets (OR 0.908 [0.841, 0.981], p = 0.0144). Enrichment analysis highlighted the association of Alpha ketoglutarate levels with five plasma metabolites in metabolic pathways relevant to stroke, specifically Arginine biosynthesis, Butanoate metabolism, Citrate cycle (TCA cycle), Alanine, aspartate, and glutamate metabolism, and Lipid acid metabolism, all linked to oxoglutaric acid.

CONCLUSION:

The discovery dataset showed the most significant positive effect of the 5'-homophase (AMP) to phase ratio, while the validation dataset revealed the most significant positive effect of the 13 HODE+9-HODE levels. Additionally, alpha ketoglutarate may offer a potential protective effect on stroke by influencing five metabolic pathways that intersect with Oxoglutaric acid during the progression of the condition.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Accidente Cerebrovascular / Análisis de la Aleatorización Mendeliana Límite: Humans Idioma: En Revista: Prog Neuropsychopharmacol Biol Psychiatry Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Accidente Cerebrovascular / Análisis de la Aleatorización Mendeliana Límite: Humans Idioma: En Revista: Prog Neuropsychopharmacol Biol Psychiatry Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido