Objective: The PPL, a class of statistics for complex trait genetic mapping in humans, utilizes Bayesian sequential updating to accumulate evidence for or against linkage across potentially heterogeneous data (sub)sets. Here, we systematically explore the relative efficacy of alternative subsetting approaches for purposes of PPL calculation. Methods: We simulated genotypes for three pedigree sets (sib pairs; 2–3 generations; ≧4 generations) based on families from an ongoing study. For each pedigree set, 100 replicates were generated under different levels of heterogeneity (1000 under ‘no linkage’). Within each replicate, updating was performed across subsets defined randomly (RAND2, RAND4), by true (TRUE) linkage status, with a realistic (REAL) classification, by individual pedigree (PED), or without any subsetting (NONE). Results: Under ‘linkage’, REAL yields larger PPLs compared to NONE, RAND2, RAND4, or PED. Under ‘no linkage’, RAND2, RAND4 and PED yield PPLs close to NONE. Conclusions: We have examined the impact of different subsetting strategies on the sampling behavior of the PPL. Our results underscore the utility of finding variables that can help delineate more homogeneous data subsets and demonstrate that, once such variables are found, sequential updating can be highly beneficial in the presence of appreciable heterogeneity at a linked locus, without inflation at an unlinked locus.
© 2008 S. Karger AG, Basel
- Complex traits
- Linkage analysis
- Genetic mapping
- Posterior probability of linkage
- Sequential updating
- Clinically defined subsets
- Bayesian linkage analysis
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Received: September 24, 2007
Accepted after revision: November 16, 2007
Published online: July 9, 2008
Number of Print Pages : 15
Number of Figures : 5, Number of Tables : 6, Number of References : 30
Human Heredity (International Journal of Human and Medical Genetics)
Vol. 66, No. 4, Year 2008 (Cover Date: October 2008)
Journal Editor: Devoto M. (Philadelphia, Pa.)
ISSN: 0001–5652 (Print), eISSN: 1423–0062 (Online)
For additional information: http://www.karger.com/HHE
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