Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals ...of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)—a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
Display omitted
•GBMI is a collaborative network of 24 biobanks with >2.2 M individuals•GWASs in different biobanks worldwide can be successfully integrated•Biobank meta-analyses identified 317 known and 183 novel loci for 14 endpoints•GBMI publicly releases summary statistics of biobank meta-analyses
Zhou et al. present the flagship project of the Global Biobank Meta-analysis Initiative (GBMI). They demonstrate the substantial benefits of the collaborative efforts of 23 biobanks worldwide to advance genetic discoveries for human diseases with larger sample sizes and increased ancestry diversity and highlight issues and challenges in biobank meta-analyses.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Meta-analysis is pervasively used to combine multiple genome-wide association studies (GWASs). Fine-mapping of meta-analysis studies is typically performed as in a single-cohort study. Here, we first ...demonstrate that heterogeneity (e.g., of sample size, phenotyping, imputation) hurts calibration of meta-analysis fine-mapping. We propose a summary statistics-based quality-control (QC) method, suspicious loci analysis of meta-analysis summary statistics (SLALOM), that identifies suspicious loci for meta-analysis fine-mapping by detecting outliers in association statistics. We validate SLALOM in simulations and the GWAS Catalog. Applying SLALOM to 14 meta-analyses from the Global Biobank Meta-analysis Initiative (GBMI), we find that 67% of loci show suspicious patterns that call into question fine-mapping accuracy. These predicted suspicious loci are significantly depleted for having nonsynonymous variants as lead variant (2.7×; Fisher’s exact p = 7.3 × 10−4). We find limited evidence of fine-mapping improvement in the GBMI meta-analyses compared with individual biobanks. We urge extreme caution when interpreting fine-mapping results from meta-analysis of heterogeneous cohorts.
Display omitted
•Extensive simulation of meta-analyses to show substantial fine-mapping miscalibration•SLALOM, a novel method that identifies suspicious loci for meta-analysis fine-mapping•Significant depletion of likely causal variants in SLALOM-predicted suspicious loci•Widespread suspicious loci for fine-mapping in current meta-analysis summary statistics
Genome-wide associations studies (GWASs), often performed as meta-analyses, have identified tens of thousands of disease-associated loci. Kanai et al. demonstrate via large-scale simulations and real data analysis that standard tools for pinpointing the causal variants underlying these associations can produce unreliable results when applied to GWAS meta-analyses.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Load filters
No result was selected!
Please select the results that you wish to export.
The search was successfully saved.
Editing
The search could not be saved.
Saved searches can be viewed in the list My searches.
The changes made to the saved search were saved successfully.
Save search
Shelf entry
No result was selected!
Adding material to shelf was successful.
Adding material to shelf was partly successful.
Adding material to shelf failed completely.
It was not necessary to add the material to the shelf.
Please select the results that you want to put on shelf!
On shelf the following records have been successfully added:
On shelf the following records have been successfully added:
