Mendelian randomization assessing causal relationship between fibrinogen levels and ischemic stroke

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.