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Improving power for rare‐variant tests by integrating external controls
dc.contributor.authorLee, Seunggeun
dc.contributor.authorKim, Sehee
dc.contributor.authorFuchsberger, Christian
dc.date.accessioned2017-10-23T17:32:07Z
dc.date.available2019-01-07T18:34:38Zen
dc.date.issued2017-11
dc.identifier.citationLee, Seunggeun; Kim, Sehee; Fuchsberger, Christian (2017). "Improving power for rare‐variant tests by integrating external controls." Genetic Epidemiology 41(7): 610-619.
dc.identifier.issn0741-0395
dc.identifier.issn1098-2272
dc.identifier.urihttps://hdl.handle.net/2027.42/138932
dc.description.abstractDue 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 combined control samples of internal and external controls. From simulation experiments and the analysis of data from age‐related macular degeneration and type 2 diabetes studies, we demonstrate that our method can substantially improve power while controlling for type I error rate.
dc.publisherSpringer
dc.publisherWiley Periodicals, Inc.
dc.subject.otherRare‐variant test
dc.subject.otherexternal controls
dc.subject.othernext‐generation sequencing
dc.titleImproving power for rare‐variant tests by integrating external controls
dc.typeArticleen_US
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelGenetics
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biology
dc.subject.hlbsecondlevelBiological Chemistry
dc.subject.hlbtoplevelHealth Sciences
dc.subject.hlbtoplevelScience
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/138932/1/gepi22057.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/138932/2/gepi22057_am.pdf
dc.identifier.doi10.1002/gepi.22057
dc.identifier.sourceGenetic Epidemiology
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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