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Mendelian randomization assessing causal relationship between fibrinogen levels and ischemic stroke

Gie Ken-Dror1, Tanya Khanna1, Emily Hills1

  • 1Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL), London TW20 0EX, UK.

Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association
|December 14, 2024
PubMed
Abstract

Insights

High fibrinogen levels significantly increase the risk of ischemic stroke (IS). Mendelian randomization confirmed that elevated fibrinogen is a causal factor, with each 1g/L rise potentially doubling stroke risk.

Area of Science:

  • Cardiovascular Genetics
  • Neurology
  • Thrombosis Research

Background:

  • Elevated plasma fibrinogen levels are a known risk factor for ischemic stroke (IS).
  • The causal relationship between fibrinogen and IS requires further investigation using robust genetic methods.

Purpose of the Study:

  • To investigate the potential causal relationship between plasma fibrinogen levels and the risk of ischemic stroke (IS) using Mendelian randomization (MR).

Main Methods:

  • A Mendelian randomization (MR) approach was employed using meta-analytically derived data.
  • The FGB rs1800790 single nucleotide polymorphism (SNP) served as an instrumental variable for fibrinogen levels.
  • Inverse-variance weighted (IVW) methods were used for primary analyses, with sensitivity analyses performed using alternative approaches.

Main Results:

  • A meta-analysis of 24 studies (20,902 cases, 76,510 controls) confirmed that the FGB rs1800790 SNP is a valid instrumental variable.
  • Individuals with specific genotypes (AG and AA) of rs1800790 exhibited significantly higher plasma fibrinogen concentrations compared to GG homozygotes.
  • Mendelian randomization analysis revealed a significant causal association between elevated fibrinogen levels and an increased risk of IS, with each 1 g/L increase in fibrinogen causally linked to a higher risk.

Conclusions:

  • Elevated plasma fibrinogen levels are confirmed as a causative risk factor for ischemic stroke (IS).
  • Each 1 g/L increase in fibrinogen concentration is associated with a substantial increase in IS risk, highlighting its clinical significance.
Keywords:
Fibrinogen levelsIschemic strokeMendelian randomizationMeta-analysis

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