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PSEUDO -- Variance estimation for the replicate pool method
An important feature of the replicate pool method is that the variance structure for the replicate pool p-value estimator (pRP) differs from
a standard gene-dropping p-value estimator (pGD). For N simulations, the distribution
of pGD will be Binomial(N, p) and
For pRP, the variance will be different because family-specific statistics are reused inducing a
correlation among simulated outcomes. Song (2004) studied the variance structure of pRP and showed that
where
When NP is large, this simplifies to
Family variance weights
Family variance weights (Wfc) represent the conditional probability that the replicate sampling for family
f on chromosome c drives the outcome of the experiment. PSEUDO estimates this values as
References
Song KK, Weeks DE, Sobel E, Feingold E (2004) Efficient Simulation of P Values for Linkage Analysis. Genetic Epidemiology 24: 1-9
Wigginton JE and Abecasis GR (2005) An Evaluation of the Replicate Pool Method : A Method for Quick Estimation of
Genomewide Linkage Peak P-Values. ...
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