Meta-analysis in genome-wide association studies.
paper
Cited
Public
- Authors
- Zeggini, Eleftheria; Ioannidis, John P A
- Year
- 2009
- Journal
- Pharmacogenomics
- PMID
- 19207020
- DOI
- 10.2217/14622416.10.2.191
- PMCID
- PMC2695132
The advent of genome-wide association studies has allowed considerable progress in the identification and robust replication of common gene variants that confer susceptibility to common diseases and other phenotypes of interest. These genetic effect sizes are almost invariably moderate to small in magnitude and single studies, even if large, are underpowered to detect them with confidence. Meta-analysis of many genome-wide association studies improves the power to detect more associations, and to investigate the consistency or heterogeneity of these associations across diverse datasets and study populations. In this review, we discuss the key methodological issues in the set-up, information gathering and processing, and analysis of meta-analyses of genome-wide association datasets. We illustrate, as an example, the application of meta-analysis methods in the elucidation of common genetic variants associated with Type 2 diabetes. Finally, we discuss the prospects and caveats for future application of meta-analysis methods in the genome-wide setting.
Typical work flow for conducting a meta-analysis of GWA datasets
LLM interpretation
This figure is a flow diagram illustrating the typical workflow for conducting a meta-analysis of genome-wide association (GWA) datasets. It depicts a linear sequence of nine steps, starting with "Set up Consortium" and ending with "Update meta-analysis for selected variants including all data." The process includes intermediate stages such as protocol writing, data harmonization, sharing association statistics, investigating heterogeneity, synthesizing results, and replicating findings.
Common meta-analysis methods
LLM interpretation
This figure is a hierarchical diagram illustrating common meta-analysis methods. It branches from a main heading into two primary categories: P-value meta-analysis and effect size meta-analysis. The effect size category is further subdivided into three approaches: fixed effects, random effects, and Bayesian meta-analysis, each with a brief description of its underlying assumptions or characteristics.
| Name | Type |
|---|---|
| 11 promising signals local | variant |
| 2.2 million SNPs local | variant |
| 69 SNPs local | variant |
| age | phenotype |
| analysis reporting bias local | phenotype |
| associated SNPs | cohort |
| asthma | phenotype |
| biobanks | cohort |
| body mass index | phenotype |
| case-control sample | cohort |
| causal variant | cohort |
| causal variants | cohort |
| common variants | cohort |
| complex diseases | phenotype |
| complex disorders | phenotype |
| consortia | cohort |
| Consortium local | cohort |
| copy number variation | variant |
| DGI local | cohort |
| different racial groups local | cohort |
| different risk populations local | cohort |
| Epidemiological Study local | cohort |
| extended replication efforts local | cohort |
| fine-mapping local | drug |
| follow-up sample sets local | cohort |
| FTO | gene |
| FUSION | cohort |
| genetic loci local | gene |
| genetic locus local | variant |
| genetic risk | cohort |
| genetic variants | cohort |
| GWA Dataset local | cohort |
| GWA datasets | cohort |
| GWA meta-analyses local | cohort |
| GWA scans local | phenotype |
| GWA study | cohort |
| GWA teams local | cohort |
| HapMap | cohort |
| International Hapmap Project | cohort |
| isolated efforts local | cohort |
| loci local | gene |
| meta-analysis | cohort |
| novel variant | cohort |
| obesity | phenotype |
| Parkinsonβs disease | phenotype |
| phenome scans local | phenotype |
| phenotype | phenotype |
| phenotype of interest | phenotype |
| publication bias local | phenotype |
| rare variant | cohort |
| replication studies local | cohort |
| selection bias | phenotype |
| selective outcome reporting bias local | phenotype |
| sex | phenotype |
| SNP | cohort |
| Stage 1 meta-analysis cohort local | cohort |
| stage 2 | cohort |
| Stage 2 replication cohort local | cohort |
| stage 3 local | cohort |
| Stage 3 replication cohort local | cohort |
| study cohort | cohort |
| targeted resequencing experiments local | drug |
| type 2 diabetes | phenotype |
| variant | cohort |
| WTCCC | cohort |
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