Combining controls can improve power in two-stage association studies
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Liley, J. (2018). Combining controls can improve power in two-stage association studies. [Journal Article]. https://doi.org/10.1186/s12863-018-0675-y
Abstract Background High dimensional case control studies are ubiquitous in the biological sciences, particularly genomics. To maximise power while constraining cost and to minimise type-1 error rates, researchers typically seek to replicate findings in a second experiment on independent cohorts before proceeding with further analyses. This can be an expensive procedure, particularly when control samples are difficult to recruit or ascertain; for example in inter-disease comparisons, or studies on degenerative diseases. Results This paper presents a method in which control (or case) samples from the discovery cohort are re-used in a replication study. The theoretical implications of this method are discussed and simulated genome-wide association study (GWAS) tests are used to compare performance against the standard approach in a range of circumstances. Using similar methods, a procedure is proposed for ‘partial replication’ using a new independent cohort consisting of only controls. This methods can be used to provide some validation of findings when a full replication procedure is not possible. The new method has differing sensitivity to confounding in study cohorts compared to the standard procedure, which must be considered in its application. Type-1 error rates in these scenarios are analytically and empirically derived, and an online tool for comparing power and error rates is provided. Conclusions In several common study designs, a shared-control method allows a substantial improvement in power while retaining type-1 error rate control. Although careful consideration must be made of all necessary assumptions, this method can enable more efficient use of data in GWAS and other applications.
External DOI: https://doi.org/10.1186/s12863-018-0675-y
This record's DOI: https://doi.org/10.17863/CAM.30543
Rights Holder: The Author(s)