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Genetic Epidemiology 30: 320332 (2006) An Evaluation of the Replicate Pool Method: Quick Estimation

Summary: Genetic Epidemiology 30: 320­332 (2006)
An Evaluation of the Replicate Pool Method: Quick Estimation
of Genome-Wide Linkage Peak p-Values
Janis E. WiggintonĂ and Gonc-alo R. Abecasis
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI
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 simu-
lations to explore properties of the replicate pool p-value estimator ^pRP 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 ^pRP 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 ^pRP 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. 30:320­332, 2006. r 2006 Wiley-Liss, Inc.


Source: Abecasis, Goncalo - Department of Biostatistics, University of Michigan


Collections: Biology and Medicine; Mathematics