title: Genetic associations with brain microbleeds: Systematic review and meta-analyses.
abstract: OBJECTIVE
  We performed a systematic review and meta-analyses to assess the evidence for genetic associations with brain microbleeds (BMBs).
  
  
  METHODS
  We sought all published studies of the association between any genetic polymorphism and BMBs studied in a total of >100 people. We critically appraised studies, and calculated pooled odds ratios (ORs) using the generic inverse variance fixed effects method. We used I² and χ² statistics to assess heterogeneity, and fail-safe N estimates to assess the robustness of our results.
  
  
  RESULTS
  Only the APOE ε2/3/4 polymorphism had been studied in >100 people (10 studies, 7,351 participants). Compared with people with the ε3/ε3 genotype, carriers of the ε4 allele (ε4+) were statistically significantly more likely to have BMBs in any location (ε4+ vs ε3/ε3: pooled OR 1.22, 95% confidence interval [CI] 1.05-1.41, p = 0.01). For strictly lobar BMBs, this association appeared slightly stronger (ε4+ vs ε3/ε3: pooled OR 1.35, 95% CI 1.10-1.66, p = 0.005). The association of ε4+ genotypes with strictly lobar BMBs was reasonably robust to potential publication and reporting biases.
  
  
  CONCLUSIONS
  Given the known associations of APOE alleles with lobar intracerebral hemorrhage and cerebral amyloid angiopathy, these findings support the concept that strictly lobar BMBs may be an imaging biomarker of cerebral amyloid angiopathy.
authors.affiliation: Medical School, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, EH4 2XU, UK.
authors.forename: S S
authors.initials: SS
authors.lastname: Maxwell
authors.forename: C A
authors.initials: CA
authors.lastname: Jackson
authors.forename: L
authors.initials: L
authors.lastname: Paternoster
authors.forename: C
authors.initials: C
authors.lastname: Cordonnier
authors.forename: V
authors.initials: V
authors.lastname: Thijs
authors.forename: R
authors.initials: R
authors.lastname: Al-Shahi Salman
authors.forename: C L M
authors.initials: CL
authors.lastname: Sudlow
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic
chemical_list: D001057:Apolipoproteins E