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Combining controls can improve power in two-stage association studies.
1Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. ajl88@medschl.cam.ac.uk.
BMC Genetics
|October 5, 2018
Summary
This study introduces a shared-control method for reusing samples in replication studies, enhancing statistical power and reducing costs in genomic research. This approach improves efficiency in genome-wide association studies (GWAS) when full replication is challenging.
Area of Science:
- Genomic studies
- Biostatistics
- Bioinformatics
Background:
- High-dimensional case-control studies are common in genomics.
- Replication studies are crucial but often expensive, especially for control samples.
- Cost and type-1 error rates are key considerations in study design.
Purpose of the Study:
- To present a novel method for reusing control or case samples in replication studies.
- To compare the performance of the new method against standard approaches using simulations.
- To propose a 'partial replication' method for situations where full replication is not feasible.
Main Methods:
- Developed a shared-control method for reusing samples in discovery and replication cohorts.
- Utilized simulated genome-wide association study (GWAS) tests for performance comparison.
- Proposed a 'partial replication' procedure using an independent cohort of controls.
Main Results:
- The shared-control method offers substantial power improvements while maintaining type-1 error rate control.
- Simulations demonstrated comparable or superior performance to standard methods in various scenarios.
- The 'partial replication' method provides validation when full replication is not possible.
Conclusions:
- The shared-control method enables more efficient data utilization in GWAS and similar studies.
- Careful consideration of assumptions is necessary for applying this method.
- This approach can lead to significant improvements in statistical power and cost-effectiveness.
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