Genetic associations with brain microbleeds: Systematic review and meta-analyses

Area of Science:

• Neurogenetics
• Neurology
• Radiology

Background:

• Brain microbleeds (BMBs) are small hemorrhages in the brain parenchyma.
• Genetic factors are increasingly recognized as potential contributors to BMBs.
• Understanding genetic associations can elucidate BMB pathogenesis.

Purpose of the Study:

• To systematically review and meta-analyze genetic associations with BMBs.
• To identify specific genetic polymorphisms linked to BMB occurrence.
• To assess the strength and robustness of these genetic associations.

Main Methods:

• Systematic literature search for studies on genetic polymorphisms and BMBs (>100 participants).
• Critical appraisal of included studies.
• Meta-analysis using fixed-effects model to calculate pooled odds ratios (ORs).
• Assessment of heterogeneity and publication bias.

Main Results:

• Only the Apolipoprotein E (APOE) polymorphism was studied in >100 participants (10 studies, 7,351 individuals).
• APOE ε4 allele carriers showed a significantly higher likelihood of BMBs (pooled OR 1.22, 95% CI 1.05-1.41).
• The association was stronger for strictly lobar BMBs (pooled OR 1.35, 95% CI 1.10-1.66).

Conclusions:

• The APOE ε4 allele is associated with an increased risk of BMBs.
• The association is more pronounced for strictly lobar BMBs.
• Strictly lobar BMBs may serve as an imaging biomarker for cerebral amyloid angiopathy.