Replication in genome-wide association studies.
paper
Cited
Public
- Authors
- Kraft, Peter; Zeggini, Eleftheria; Ioannidis, John P A
- Year
- 2009
- Journal
- Statistical science : a review journal of the Institute of Mathematical Statistics
- PMID
- 20454541
- DOI
- 10.1214/09-STS290
- PMCID
- PMC2865141
Replication helps ensure that a genotype-phenotype association observed in a genome-wide association (GWA) study represents a credible association and is not a chance finding or an artifact due to uncontrolled biases. We discuss prerequisites for exact replication; issues of heterogeneity; advantages and disadvantages of different methods of data synthesis across multiple studies; frequentist vs. Bayesian inferences for replication; and challenges that arise from multi-team collaborations. While consistent replication can greatly improve the credibility of a genotype-phenotype association, it may not eliminate spurious associations due to biases shared by many studies. Conversely, lack of replication in well-powered follow-up studies usually invalidates the initially proposed association, although occasionally it may point to differences in linkage disequilibrium or effect modifiers across studies.
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| 40 | 6. The wider picture of replication efforts: consortia, data availability, and field synopses | In silico replication of association signals has been further facilitated by initiatives making⦠|
| 41 | 6. The wider picture of replication efforts: consortia, data availability, and field synopses | Replication undoubtedly constitutes an evolving practice. The need to incorporate new data arising⦠|
| 42 | 6. The wider picture of replication efforts: consortia, data availability, and field synopses β 6.i. Example from the field of type 2 diabetes | Researchers in the field of type 2 diabetes (T2D) genetics were among the first to lead the way inβ¦ |
| 43 | 6. The wider picture of replication efforts: consortia, data availability, and field synopses β 6.i. Example from the field of type 2 diabetes | inconsistency in observed associations could be ascribed to study design and, specifically, toβ¦ |
| 44 | 6. The wider picture of replication efforts: consortia, data availability, and field synopses β 6.ii. Anthropometrics and the analysis of βsecondary traitsβ | The meta-analyses of body mass index and height conducted by the Genetic Investigation ofβ¦ |
| 45 | 6. The wider picture of replication efforts: consortia, data availability, and field synopses β 6.ii. Anthropometrics and the analysis of βsecondary traitsβ | the strength of the association between the secondary trait and disease (which could be modest orβ¦ |
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