An evaluation of the replicate pool method: quick estimation of genome-wide linkage peak p -values

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dc.contributor.author Wigginton, Janis E. en_US
dc.contributor.author Abecasis, Gonçalo R. en_US
dc.date.accessioned 2007-05-02T14:16:57Z
dc.date.available 2007-05-02T14:16:57Z
dc.date.issued 2006-05 en_US
dc.identifier.citation Wigginton, Janis E.; Abecasis, GonÇalo R. (2006). "An evaluation of the replicate pool method: quick estimation of genome-wide linkage peak p -values." Genetic Epidemiology 30(4): 320-332. <http://hdl.handle.net/2027.42/50657> en_US
dc.identifier.issn 0741-0395 en_US
dc.identifier.issn 1098-2272 en_US
dc.identifier.uri http://hdl.handle.net/2027.42/50657
dc.identifier.uri http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16832873&dopt=citation en_US
dc.description.abstract The calculation of empirical p -values for genome-wide non-parametric linkage tests continues to present significant computational challenges for many complex disease mapping studies. The gold standard approach is to use gene dropping to simulate null genome scans. Unfortunately, this approach is too computationally expensive for many data sets of interest. An alternative, more efficient method for sampling null genome scans is to pre-calculate pools of family-specific statistics and then resample from these replicate pools to generate “pseudo-replicate” genome scans. In this study, we use simulations to explore properties of the replicate pool p -value estimator [pcirc] RP and show that it provides an excellent approximation to the traditional gene-dropping estimator for significantly less computational effort. While the computational efficiency of the replicate pool estimator is noticeable in almost all data sets, by applying the replicate pool method to several previously characterized data sets we show that savings in computational effort can be especially significant (on the order of 10,000-fold or more) when one or more large families are analyzed. We also estimate replicate pool p -values for the schizophrenia data described by Abecasis et al. and show that [pcirc] RP closely approximates gene-drop p -values for all linkage peaks reported for this study. Lastly, we expand upon Song et al.'s previous work by deriving a conservative estimator of the variance for [pcirc] RP that can easily be computed in practical settings.We have implemented the replicate pool method along with our variance estimator in a new program called Pseudo, which is the first widely available automated implementation of the replicate pool method. Genet . Epidemiol . 30, 2006. © 2006 Wiley-Liss, Inc. en_US
dc.format.extent 301998 bytes
dc.format.extent 3118 bytes
dc.format.mimetype application/pdf
dc.format.mimetype text/plain
dc.publisher Wiley Subscription Services, Inc., A Wiley Company en_US
dc.subject.other Life and Medical Sciences en_US
dc.subject.other Genetics en_US
dc.title An evaluation of the replicate pool method: quick estimation of genome-wide linkage peak p -values en_US
dc.type Article en_US
dc.rights.robots IndexNoFollow en_US
dc.subject.hlbsecondlevel Biological Chemistry en_US
dc.subject.hlbsecondlevel Genetics en_US
dc.subject.hlbsecondlevel Molecular, Cellular and Developmental Biology en_US
dc.subject.hlbtoplevel Health Sciences en_US
dc.subject.hlbtoplevel Science en_US
dc.description.peerreviewed Peer Reviewed en_US
dc.contributor.affiliationum Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI ; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI en_US
dc.contributor.affiliationum Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI en_US
dc.identifier.pmid 16832873 en_US
dc.description.bitstreamurl http://deepblue.lib.umich.edu/bitstream/2027.42/50657/1/20147_ftp.pdf en_US
dc.identifier.doi http://dx.doi.org/10.1002/gepi.20147 en_US
dc.identifier.source Genetic Epidemiology en_US
dc.owningcollname Interdisciplinary and Peer-Reviewed
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