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Related Concept Videos

Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

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Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
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Updated: Jun 14, 2025

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Causal relationship between genetically determined plasma metabolites and stroke: A two sample Mendelian

Yi Huang1, Siqi Chen1, Enhao Zhang1

  • 1Ningbo 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.

Progress in Neuro-Psychopharmacology & Biological Psychiatry
|September 2, 2024
PubMed
Summary

This study explored plasma metabolites and stroke risk. Alpha ketoglutarate showed a protective effect, potentially influencing key metabolic pathways involved in stroke.

Keywords:
CausalMendelian randomizationMetabolitesOsteoarthritisTwo-sample

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Area of Science:

  • Biochemistry
  • Genetics
  • Epidemiology

Background:

  • Investigating the causal links between plasma metabolites and stroke incidence.
  • Understanding the role of biochemical markers in cerebrovascular disease.

Purpose of the Study:

  • To identify specific plasma metabolites causally associated with stroke risk.
  • To explore potential therapeutic targets for stroke prevention through metabolic interventions.

Main Methods:

  • Utilized Mendelian randomization (MR) with inverse variance weighted (IVW), weighted median (WM), and MR Egger methods.
  • Validated findings using the Steiger test, LD linkage disequilibrium score, and UK Biobank data.

Main Results:

  • Identified significant associations for X-17335 (negative) and 5'-homophase (AMP) to phase ratio (positive).
  • Alpha ketoglutarate demonstrated a consistent protective causal effect on stroke across discovery and validation datasets.
  • Enrichment analysis linked alpha ketoglutarate to five stroke-relevant metabolic pathways, including the TCA cycle and lipid metabolism.

Conclusions:

  • Alpha ketoglutarate may offer a protective effect against stroke.
  • Metabolic pathways involving alpha ketoglutarate (linked to oxoglutaric acid) are crucial in stroke progression.
  • Findings suggest potential for metabolic biomarkers and interventions in stroke prevention.