Genetically Elevated Neutrophil Count Is Associated with Poor Outcome Following Ischemic Stroke: A Mendelian...

Area of Science:

• Genetics
• Neurology
• Immunology

Background:

• Ischemic stroke significantly impacts functional outcomes.
• White blood cell (WBC) subtypes are implicated in inflammatory responses post-stroke.
• Understanding genetic influences on WBC counts could reveal novel therapeutic targets.

Purpose of the Study:

• To investigate the association between genetically proxied WBC subtype counts and functional outcome after ischemic stroke.
• To determine if genetic predisposition to higher neutrophil counts correlates with poorer stroke recovery.

Main Methods:

• Utilized summary-level data from large-scale genome-wide association studies (GWAS) for WBC counts and ischemic stroke functional outcomes.
• Employed Mendelian randomization (MR) analysis, including univariable and multivariable approaches.
• Defined poor functional outcome as a modified Rankin Scale (mRS) score > 2 at 3 months post-stroke.

Main Results:

• Genetically proxied higher neutrophil count showed a nominal association with poor functional outcome (OR=1.33, P=0.020).
• This association remained significant in multivariable MR analysis adjusting for other WBC subtypes (OR=1.45, P=0.021).
• No significant associations were found for other WBC subtypes (lymphocytes, monocytes, eosinophils, basophils).

Conclusions:

• Genetic evidence suggests a link between higher neutrophil counts and adverse functional outcomes following ischemic stroke.
• Neutrophils may represent a potential therapeutic target for improving stroke recovery.
• Further research is warranted to confirm these findings and elucidate underlying molecular mechanisms.