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Importance sampling method of correction for multiple testing in affected sib-pair linkage analysis
Authors:Klein Alison P  Kovac Ilija  Sorant Alexa J M  Baffoe-Bonnie Agnes  Doan Betty Q  Ibay Grace  Lockwood Erica  Mandal Diptasri  Santhosh Lekshmi  Weissbecker Karen  Woo Jessica  Zambelli-Weiner April  Zhang Jie  Naiman Daniel Q  Malley James  Bailey-Wilson Joan E
Affiliation:Inherited Disease Research Branch, NHGRI, NIH, Baltimore, Maryland, USA. aklein@nhgri.nih.gov
Abstract:Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and na?ve Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods. The type I error rates for each correction method and the ability of each of the methods to detect loci known to influence trait values were compared. All of the methods considered were conservative with respect to type I error, especially the Bonferroni method. The ability of these methods to detect trait loci was also low. However, this may be partially due to a limitation inherent in our binary trait definitions.
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