JSM 2005 - Toronto

Abstract #303405

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Legend: = Applied Session, = Theme Session, = Presenter
Activity Number: 277
Type: Contributed
Date/Time: Tuesday, August 9, 2005 : 10:30 AM to 12:20 PM
Sponsor: Biometrics Section
Abstract - #303405
Title: The Probability of Type-I Error when Maximizing Multipoint Lod Scores over Model Parameters: A Simulation Study
Author(s): Chao Xing*+ and Robert C. Elston
Companies: Case Western Reserve University and Case Western Reserve University
Address: Wolstein Research Building, Cleveland, OH, 44143, United States
Keywords: type I error ; mod score ; multipoint linkage
Abstract:

The probability of type-I error and methods of correcting for multiple testing when maximizing single-point lod scores over both the recombination fraction and genetic model parameters have been widely investigated. The mod score method has been recommended not only for detecting linkage, but for inferring the mode of inheritance of a disease locus. However, in the case of multipoint lod scores, where the likelihood is not maximized over the recombination fraction, the asymptotic theory for single-point lod scores no longer applies. In this study, we simulate a map of two markers 10 cm apart and one unlinked disease locus under both dominant and recessive models with reduced penetrances of 0.8, 0.5, and 0.2. We analyzed the data under both dominant and recessive models with penetrances ranging from 0.1 to 0.9 by multipoint linkage analysis. The results show the probability of type-I error depends on the specified genetic model. Low penetrance models tend to generate more false positive results than high penetrance models. Therefore, when employing the multipoint lod (or mod) score approach, caution should be taken in specifying (or inferring) the genetic model.

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Revised March 2005