Dataset Information

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 ?² statistics to assess heterogeneity, and fail-safe N estimates to assess the robustness of our results.

Results

Only the APOE ?2/3/4 polymorphism had been studied in >100 people (10 studies, 7,351 participants). Compared with people with the ?3/?3 genotype, carriers of the ?4 allele (?4+) were statistically significantly more likely to have BMBs in any location (?4+ vs ?3/?3: pooled OR 1.22, 95% confidence interval [CI] 1.05-1.41, p = 0.01). For strictly lobar BMBs, this association appeared slightly stronger (?4+ vs ?3/?3: pooled OR 1.35, 95% CI 1.10-1.66, p = 0.005). The association of ?4+ 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.

SUBMITTER: Maxwell SS

PROVIDER: S-EPMC3140069 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Maxwell S S SS Jackson C A CA Paternoster L L Cordonnier C C Thijs V V Al-Shahi Salman R R Sudlow C L M CL

Neurology 20110629 2

<h4>Objective</h4>We performed a systematic review and meta-analyses to assess the evidence for genetic associations with brain microbleeds (BMBs).<h4>Methods</h4>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 ...[more]

PMID: 21715706

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Project description:Genetic association studies on schizophrenia (SZ) have been repeatedly performed over the last two decades, resulting in a consensus that results are generally inconsistent. This consensus has begun to change as a result of meta-analyses (e.g., [Glatt, S.J. and Jonsson, E.G., 2006. The Cys allele of the DRD2 Ser311Cys polymorphism has a dominant effect on risk for schizophrenia: evidence from fixed- and random-effects meta-analyses. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 141, 149-154.]). The SchizophreniaGene database (http://www.schizophreniaforum.org/res/sczgene/default.asp) has been a leader in meta-analyses of SZ association data, by dynamically and comprehensively cataloging all public genetic association studies, and preparing meta-analyses of case-control data. There are 19 "top" candidate genes from these analyses (access on December 20, 2007), showing the highest effect sizes and nominally significant associations of at least one variant in the meta-analyses of all ethnic samples or of samples of Caucasian ancestry. We selected 40 polymorphisms in 12 selected "top" genes for additional meta-analyses, which had at least one familial association data. We found gene-wide (correction for the number of meta-analyses for each gene) significant allelic association evidence for seven genes in the combined samples. The odds ratios (ORs) of the associated minor risk alleles range from 1.072 to 1.121, for DRD4, MTHFR, PPP3CC and TP53. For protective allele associations, the ORs are between 0.842 and 0.886, for DAO, IL1B, and SLC6A4. In population-based sub-analyses, we found significant results in four genes in Asians (ORs between 1.084 and 1.309 for DRD4, GABRB2, PPP3CC, and TP53), and one gene in European (OR of 0.888 for SLC6A4). The association of rs1816072 of GABRB2 with SZ in Asians was significant (adjusted P=0.048 after correction for 80 tests). No significant heterogeneity between case-control and family-based study designs was detected in 35 out of 40 polymorphisms. Our results further support eight potential SZ candidate genes and suggest that family data can reasonably be included in the meta-analysis of genetic associations.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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