Improving power for rare-variant tests by integrating external controls.

ABSTRACT: Due to the drop in sequencing cost, the number of sequenced genomes is increasing rapidly. To improve power of rare-variant tests, these sequenced samples could be used as external control samples in addition to control samples from the study itself. However, when using external controls, possible batch effects due to the use of different sequencing platforms or genotype calling pipelines can dramatically increase type I error rates. To address this, we propose novel summary statistics based single and gene- or region-based rare-variant tests that allow the integration of external controls while controlling for type I error. Our approach is based on the insight that batch effects on a given variant can be assessed by comparing odds ratio estimates using internal controls only vs. using com

SUBMITTER: Lee S 

PROVIDER: S-EPMC6082405 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature